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1.	Abelein, Axel, 1985-, et al. (författare) Corrigendum to “Transient small molecule interactions kinetically modulate amyloid β peptide self-assembly” [FEBS Lett. 586 (2012) 3991–3995] 2013 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 587:9, s. 1452-1452 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
2.	Abelein, Axel, et al. (författare) Transient small molecule interactions kinetically modulate amyloid beta peptide self-assembly 2012 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 586:22, s. 3991-3995 Tidskriftsartikel (refereegranskat)abstract Small organic molecules, like Congo red and lacmoid, have been shown to modulate the self-assembly of the amyloid beta peptide (A beta). Here, we show that A beta forms NMR invisible non-toxic co-aggregates together with lacmoid as well as Congo red. We find that the interaction involves two distinct kinetic processes and at every given time point only a small fraction of A beta is in the co-aggregate. These weak transient interactions kinetically redirect the aggregation prone A beta from self-assembling into amyloid fibrils. These findings suggest that even such weak binders might be effective as therapeutics against pathogenic protein aggregation.
3.	Abelein, Axel, et al. (författare) Transient small molecule interactions kinetically modulate amyloid β peptide self-assembly. 2012 Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 586:22, s. 3991-3995 Tidskriftsartikel (refereegranskat)abstract Small organic molecules, like Congo red and lacmoid, have been shown to modulate the self-assembly of the amyloid β peptide (Aβ). Here, we show that Aβ forms NMR invisible non-toxic co-aggregates together with lacmoid as well as Congo red. We find that the interaction involves two distinct kinetic processes and at every given time point only a small fraction of Aβ is in the co-aggregate. These weak transient interactions kinetically redirect the aggregation prone Aβ from self-assembling into amyloid fibrils. These findings suggest that even such weak binders might be effective as therapeutics against pathogenic protein aggregation.
4.	Ahmadpour, Doryaneh, 1973, et al. (författare) The mitogen-activated protein kinase Slt2 modulates arsenite transport through the aquaglyceroporin Fps1 2016 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 590:20, s. 3649-3659 Tidskriftsartikel (refereegranskat)abstract © 2016 Federation of European Biochemical Societies Arsenite is widely present in nature; therefore, cells have evolved mechanisms to prevent arsenite influx and promote efflux. In yeast (Saccharomyces cerevisiae), the aquaglyceroporin Fps1 mediates arsenite influx and efflux. The mitogen-activated protein kinase (MAPK) Hog1 has previously been shown to restrict arsenite influx through Fps1. In this study, we show that another MAPK, Slt2, is transiently phosphorylated in response to arsenite influx. Our findings indicate that the protein kinase activity of Slt2 is required for its role in arsenite tolerance. While Hog1 prevents arsenite influx via phosphorylation of T231 at the N-terminal domain of Fps1, Slt2 promotes arsenite efflux through phosphorylation of S537 at the C terminus. Our data suggest that Slt2 physically interacts with Fps1 and that this interaction depends on phosphorylation of S537. We hypothesize that Hog1 and Slt2 may affect each other's binding to Fps1, thereby controlling the opening and closing of the channel.
5.	Andersson, Lotta E., et al. (författare) Glycogen metabolism in the glucose-sensing and supply-driven β-cell 2016 Ingår i: FEBS Letters. - : Wiley. - 0014-5793. ; 590:23, s. 4242-4251 Tidskriftsartikel (refereegranskat)abstract Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined.
6.	Arjona, Davinia, et al. (författare) Nitric oxide is a potent inhibitor of the cbb(3)-type heme-copper oxidases 2015 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 589:11, s. 1214-1218 Tidskriftsartikel (refereegranskat)abstract C-type heme-copper oxidases terminate the respiratory chain in many pathogenic bacteria, and will encounter elevated concentrations of NO produced by the immune defense of the host. Thus, a decreased sensitivity to NO in C-type oxidases would increase the survival of these pathogens. Here we have compared the inhibitory effect of NO in C-type oxidases to that in the mitochondrial A-type. We show that O-2-reduction in both the Rhodobacter sphaeroides and Vibrio cholerae C-type oxidases is strongly and reversibly inhibited by submicromolar NO, with an inhibition pattern similar to the A-type. Thus, NO tolerance in pathogens with a C-type terminal oxidase has to rely mainly on other mechanisms.
7.	Arnling Bååth, Jenny, 1987, et al. (författare) A glucuronoyl esterase from Acremonium alcalophilum cleaves native lignin-carbohydrate ester bonds 2016 Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 590:16, s. 2611-2618 Tidskriftsartikel (refereegranskat)abstract The Glucuronoyl esterases (GE) have been proposed to target lignin-carbohydrate (LC) ester bonds between lignin moieties and glucuronic acid side groups of xylan, but to date, no direct observations of enzymatic cleavage on native LC ester bonds have been demonstrated. In the present investigation, LCC fractions from spruce and birch were treated with a recombinantly produced GE originating from Acremonium alcalophilum (AaGE1). A combination of size exclusion chromatography and 31P NMR analyses of phosphitylated LCC samples, before and after AaGE1 treatment provided the first evidence for cleavage of the LC ester linkages existing in wood.
8.	Babazadeh, Roja, et al. (författare) The Ashbya gossypiiEF-1α promoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae. 2011 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. Tidskriftsartikel (refereegranskat)abstract Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rather than the tags per se. This promoter is frequently used in heterologous marker cassettes, including HIS3MX, KanMX, NatMX, PatMX and HphMX. Toxicity could be eliminated by promoter replacement or exclusion of the marker cassette. To our knowledge, this is the first report of toxicity caused by introduction of a heterologous promoter alone.
9.	Beebo, Azeez, 1979, et al. (författare) Assessment of the requirement for aquaporins in the thylakoid membrane of plant chloroplasts to sustain photosynthetic water oxidation 2013 Ingår i: Febs Letters. - : Wiley. - 0014-5793. ; 587:14, s. 2083-2089 Tidskriftsartikel (refereegranskat)abstract Oxygenic photosynthetic organisms use sunlight energy to oxidize water to molecular oxygen. This process is mediated by the photosystem II complex at the lumenal side of the thylakoid membrane. Most research efforts have been dedicated to understanding the mechanism behind the unique water oxidation reactions, whereas the delivery pathways for water molecules into the thylakoid lumen have not yet been studied. The most common mechanisms for water transport are simple diffusion and diffusion facilitated by specialized channel proteins named aquaporins. Calculations using published data for plant chloroplasts indicate that aquaporins are not necessary to sustain water supply into the thylakoid lumen at steady state photosynthetic rates. Yet, arguments for their presence in the plant thylakoid membrane and beneficial action are presented.
10.	Birtele, Marcella, et al. (författare) Dual modulation of neuron-specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons 2019 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:23, s. 3370-3380 Tidskriftsartikel (refereegranskat)abstract Direct neuronal reprogramming can be achieved using different approaches: by expressing neuronal transcription factors or microRNAs; and by knocking down neuronal repressive elements. However, there still exists a high variability in terms of the quality and maturity of the induced neurons obtained, depending on the reprogramming strategy employed. Here, we evaluate different long-term culture conditions and study the effect of expressing the neuronal-specific microRNAs, miR124 and miR9/9*, while reprogramming with forced expression of the transcription factors Ascl1, Brn2, and knockdown of the neuronal repressor REST. We show that the addition of microRNAs supports neuronal maturation in terms of gene and protein expression, as well as in terms of electrophysiological properties.
11.	Björkholm, Patrik, et al. (författare) Why mitochondria need a genome revisited 2017 Ingår i: FEBS Letters. - : WILEY-BLACKWELL. - 0014-5793 .- 1873-3468. ; 591:1, s. 65-75 Tidskriftsartikel (refereegranskat)abstract In this paper, we experimentally address the debate about why functional transfer of mitochondrial genes to the nucleus has been halted in some organismal groups and why cytosolic expression of mitochondrial proteins has proven remarkably difficult. By expressing all 13 human mitochondrial-encoded genes with strong mitochondrial-targeting sequences in the cytosol of human cells, we show that all proteins, except ATP8, are transported to the endoplasmic reticulum (ER). These results confirm and extend previous findings based on three mitochondrial genes lacking mitochondrial-targeting sequences that also were relocated to the ER during cytosolic expression. We conclude that subcellular protein targeting constitutes a major barrier to functional transfer of mitochondrial genes to the nuclear genome.
12.	Braun, Bernhard, et al. (författare) Gid9, a second RING finger protein contributes to the ubiquitin ligase activity of the Gid complex required for catabolite degradation 2011 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 585:24, s. 3856-3861 Tidskriftsartikel (refereegranskat)abstract The two major antagonistic pathways of carbon metabolism in cells, glycolysis and gluconeogenesis, are tightly regulated. In the eukaryotic model organism Saccharomyces cerevisiae the switch from gluconeogenesis to glycolysis is brought about by proteasomal degradation of the gluconeogenic enzyme fructose-1,6-bisphosphatase. The ubiquitin ligase responsible for polyubiquitylation of fructose-1,6-bisphosphatase is the Gid complex. This complex consists of seven subunits of which subunit Gid2/Rmd5 contains a RING finger domain providing E3 ligase activity. Here we identify an additional subunit containing a degenerated RING finger, Gid9/Fyv10. This subunit binds to Gid2/Rmd5. A mutation in the degenerated RING finger of Gid9/Fyv10 abolishes polyubiquitylation and degradation of three enzymes specific for gluconeogenesis. Structured summary of protein interactions: Gid2 physically interacts with Gid9 by anti tag coimmunoprecipitation (View interaction) (C) 2011 Federation of European Biochemical Societies.
13.	Brännström, Kristoffer, et al. (författare) The role of histidines in amyloid β fibril assembly 2017 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 591:8, s. 1167-1175 Tidskriftsartikel (refereegranskat)abstract Low pH has a strong stabilising effect on the fibrillar assembly of amyloid β, which is associated with Alzheimer's disease. The stabilising effect is already pronounced at pH 6.0, suggesting that protonation of histidines might mediate this effect. Through the systematic substitution of the three native histidines in Aβ for alanines, we have evaluated their role in fibril stability. Using surface plasmon resonance, we show that at neutral pH the fibrillar forms of all His-Ala variants are destabilised by a factor of 4-12 compared to wild-type Aβ. However, none of the His-Ala Aβ variants impair the stabilising effect of the fibril at low pH.
14.	Bykov, VJN, et al. (författare) Mutant p53 reactivation by small molecules makes its way to the clinic 2014 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 588:16, s. 2622-2627 Tidskriftsartikel (refereegranskat)
15.	Caja, Laia Puigsubira, et al. (författare) Transforming growth factor beta and bone morphogenetic protein actions in brain tumors 2015 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 589:14, s. 1588-1597 Forskningsöversikt (refereegranskat)abstract Members of the transforming growth factor beta (TGF-beta) family are implicated in the biology of several cancers. Here we focus on malignancies of the brain and examine the TGF beta and the bone morphogenetic protein (BMP) signaling branches of the family. These pathways exhibit context-dependent actions during tumorigenesis, acting either as tumor suppressors or as pro-tumorigenic agents. In the brain, the TGF-beta s associate with oncogenic development and progression to the more malignant state. Inversely, the BMPs suppress tumorigenic potential by acting as agents that induce tumor cell differentiation. The latter has been best demonstrated in grade IV astrocytomas, otherwise known as glioblastoma multiforme. We discuss how the actions of TGF-beta s and BMPs on cancer stem cells may explain their effects on tumor progression, and try to highlight intricate mechanisms that may link tumor cell differentiation to invasion. The focus on TGF-beta and BMP and their actions in brain malignancies provides a rich territory for mechanistic understanding of tumor heterogeneity and suggests ways for improved therapeutic intervention, currently being addressed by clinical trials.
16.	Christiansen, Alexander, 1982-, et al. (författare) Synthetic crowding agent dextran causes excluded volume interactions exclusively to tracer protein apoazurin 2014 Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 588:5, s. 811-814 Tidskriftsartikel (refereegranskat)abstract To understand protein biophysics in crowded cellular environments, researchers often use synthetic polymers as 'crowding agents' in vitro. The idea is that these agents will occupy space and reproduce the in vivo scenario in terms of excluded volume. However, recent work has challenged this concept and pointed out that attractive interactions between protein and crowding agent will provide an enthalpic contribution to the overall effect on protein thermodynamics. Here we use a typical synthetic crowding agent and a well-studied model protein to demonstrate in a window of 50 K that the presence of dextran 20 affects apoazurin by steric repulsion. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
17.	Cuviello, Flavia, et al. (författare) Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug-resistance associated protein 6 (MRP6) 2015 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 589:24, s. 3921-3928 Tidskriftsartikel (refereegranskat)abstract The function of the ATP-binding cassette transporter MRP6 is unknown but mutations in its gene cause pseudoxanthoma elasticum. We have investigated the membrane topology of the N-terminal transmembrane domain TMD0 of MRP6 and the membrane integration and orientation propensities of its transmembrane segments (TMs) by glycosylation mapping. Results demonstrate that TMD0 has five TMs, an Nout-Cin topology and that the less hydrophobic TMs have strong preference for their orientation in the membrane that affects the neighboring TMs. Two disease-causing mutations changing the number of positive charges in the loops of TMD0 did not affect the membrane insertion efficiencies of the adjacent TMs.
18.	Cymer, Florian, et al. (författare) Weak pulling forces exerted on N-in-orientated transmembrane segments during co-translational insertion into the inner membrane of Escherichia coli 2014 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 588:10, s. 1930-1934 Tidskriftsartikel (refereegranskat)abstract Transmembrane helices (TMHs) in membrane proteins can be orientated with their N-terminus towards the cytoplasm (N-in), or facing the non-cytoplasmic side (N-out). Most membrane proteins are inserted co-translationally into membranes, aided by Sec-type translocons. Since the final orientation of N-in-and N-out-orientated TMHs differs, they could also interact differently with the translocon and the surrounding membrane during insertion. We measured pulling forces exerted on N-in-orientated TMHs during co-translational insertion into the inner membrane of Escherichia coli. Our results demonstrate that Nin-orientated TMHs experience a weaker pulling force but retain the overall biphasic force profile seen previously for Nout-orientated TMHs (Ismail et al., 2012 [1]).
19.	Czegeny, G., et al. (författare) Hydrogen peroxide contributes to the ultraviolet-B (280-315 nm) induced oxidative stress of plant leaves through multiple pathways 2014 Ingår i: Febs Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 588:14, s. 2255-2261 Tidskriftsartikel (refereegranskat)abstract Solar UV-B (280-315 nm) radiation is a developmental signal in plants but may also cause oxidative stress when combined with other environmental factors. Using computer modeling and in solution experiments we show that UV-B is capable of photosensitizing hydroxyl radical production from hydrogen peroxide. We present evidence that the oxidative effect of UV-B in leaves is at least twofold: (i) it increases cellular hydrogen peroxide concentrations, to a larger extent in pyridoxine antioxidant mutant pdx1.3-1 Arabidopsis and; (ii) is capable of a partial photo-conversion of both 'natural' and 'extra' hydrogen peroxide to hydroxyl radicals. As stress conditions other than UV can increase cellular hydrogen peroxide levels, synergistic deleterious effects of various stresses may be expected already under ambient solar UV-B. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
20.	Daniel, Michael G., et al. (författare) Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture 2019 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:23, s. 3266-3287 Tidskriftsartikel (refereegranskat)abstract Transcription factor (TF)-based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial-like precursors that generate hematopoietic stem progenitor (HSPC)-like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC-like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell frequency. Altogether, we demonstrate an improved human hemogenic induction protocol that could provide a valuable human in vitro model of hematopoiesis for disease modeling and a platform for cell-based therapeutics. Database: Gene expression data are available in the Gene Expression Omnibus (GEO) database under the accession number GSE130361.
21.	Davies, James S, et al. (författare) Functional and solution structure studies of amino sugar deacetylase and deaminase enzymes from Staphylococcus aureus 2019 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:1, s. 52-66 Tidskriftsartikel (refereegranskat)abstract N‐Acetylglucosamine‐6‐phosphate deacetylase (NagA) and glucosamine‐6‐phosphate deaminase (NagB) are branch point enzymes that direct amino sugars into different pathways. For Staphylococcus aureus NagA, analytical ultracentrifugation and small‐angle X‐ray scattering data demonstrate that it is an asymmetric dimer in solution. Initial rate experiments show hysteresis, which may be related to pathway regulation, and kinetic parameters similar to other bacterial isozymes. The enzyme binds two Zn2+ ions and is not substrate inhibited, unlike the Escherichia coli isozyme. S. aureus NagB adopts a novel dimeric structure in solution and shows kinetic parameters comparable to other Gram‐positive isozymes. In summary, these functional data and solution structures are of use for understanding amino sugar metabolism in S. aureus, and will inform the design of inhibitory molecules.
22.	Dennissen, FJA, et al. (författare) Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3) 2011 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 585:16, s. 2568-2574 Tidskriftsartikel (refereegranskat)
23.	Duell, Ben, et al. (författare) Host–pathogen interactions of nontypeable Haemophilus influenzae : from commensal to pathogen 2016 Ingår i: FEBS Letters. - : Wiley. - 0014-5793. ; 590:21, s. 3840-3853 Forskningsöversikt (refereegranskat)abstract Nontypeable Haemophilus influenzae (NTHi) is a commensal microbe often isolated from the upper and lower respiratory tract. This bacterial species can cause sinusitis, acute otitis media in preschool children, exacerbations in patients suffering from chronic obstructive pulmonary disease, as well as conjunctivitis and bacteremia. Since the introduction of a vaccine against H. influenzae serotype b in the 1990s, the burden of H. influenzae-related infections has been increasingly dominated by NTHi. Understanding the ability of NTHi to cause infection is currently an expanding area of study. NTHi is able to exert differential binding to the host tissue through the use of a broad range of adhesins. NTHi survival in the host is multifaceted, that is, using virulence factors involved in complement resistance, biofilm, modified immunoglobulin responses, and, finally, formation and utilization of host proteins as a secondary strategy of increasing the adhesive ability.
24.	Farías-Rico, José Arcadio, et al. (författare) Mutational analysis of protein folding inside the ribosome exit tunnel 2017 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 591:1, s. 155-163 Tidskriftsartikel (refereegranskat)abstract Recent work has demonstrated that cotranslational folding of proteins or protein domains in, or in the immediate vicinity of, the ribosome exit tunnel generates a pulling force on the nascent polypeptide chain that can be detected using a so-called translational arrest peptide (AP) engineered into the nascent chain as a force sensor. Here, we show that AP-based force measurements combined with systematic Ala and Trp scans of a zinc-finger domain that folds in the exit tunnel can be used to identify the residues that are critical for intraribosomal folding. Our results suggest a general approach to characterize the folded state(s) that may form as a protein domain moves progressively down the ribosome exit tunnel.
25.	Farkas, Daniel, 1980, et al. (författare) Thioredoxin-mediated reduction of the photosystem I subunit PsaF and activation through oxidation by the interaction partner plastocyanin 2011 Ingår i: FEBS Letters. - : Wiley. - 0014-5793. ; 585, s. 1753-1758 Tidskriftsartikel (refereegranskat)
26.	Ferreira, Raphael, 1990, et al. (författare) Exploiting off-targeting in guide-RNAs for CRISPR systems for simultaneous editing of multiple genes 2017 Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 591:20, s. 3288-3295 Tidskriftsartikel (refereegranskat)abstract Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple genes simultaneously with a single gRNA. We termed these gRNAs as promiscuous gRNAs. Here, we present a computational workflow to identify promiscuous gRNAs that putatively bind to the region of interest for a defined list of genes in a genome. We experimentally validated two promiscuous gRNA for gene deletion, one targeting FAA1 and FAA4 and one targeting PLB1 and PLB2, thus demonstrating that multiplexed genome editing through design of promiscuous gRNA can be performed in a time and cost-effective manner.
27.	Frick, Anna, 1982, et al. (författare) Structural basis for pH gating of plant aquaporins 2013 Ingår i: Febs Letters. - : Wiley. - 0014-5793. ; 587:7, s. 989-993 Tidskriftsartikel (refereegranskat)abstract Plants have evolved to cope with fluctuations in water supply by gating their water channels known
28.	Furukawa, Kentaro, et al. (författare) Fungal fludioxonil sensitivity is diminished by a constitutively active form of the group III histidine kinase 2012 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 586:16, s. 2417-2422 Tidskriftsartikel (refereegranskat)abstract The fungicide fludioxonil is used to control plant-pathogenic fungi by causing improper activation of the Hog1-type MAPK. However, the appearance of fludioxonil resistant mutants, mostly caused by mutations in the group III histidine kinases, poses a serious problem. Moreover, such mutations cause also hyperosmotic sensitivity and the underlying mechanism has been elusive for a long time. Using Saccharomyces cerevisiae as an experimental host, we show that those phenotypes are conferred by a constitutively active form of the group III histidine kinase. Our results explain the different reasons for fludioxonil resistance conferred by its deletion and missense mutation.
29.	Gao, JC, et al. (författare) A feedback regulation between Kindlin-2 and GLI1 in prostate cancer cells 2013 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 587:6, s. 631-638 Tidskriftsartikel (refereegranskat)
30.	Garrido-Urbani, Sarah, et al. (författare) Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin 2016 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 590:1, s. 3-12 Tidskriftsartikel (refereegranskat)abstract Syntenin has crucial roles in cell adhesion, cell migration and synaptic transmission. Its closely linked postsynaptic density-95, discs large 1, zonula occludens-1 (PDZ) domains typically interact with C-terminal ligands. We profile syntenin PDZ1-2 through proteomic peptide phage display (ProP-PD) using a library that displays C-terminal regions of the human proteome. The protein recognizes a broad range of peptides, with a preference for hydrophobic motifs and has a tendency to recognize cryptic internal ligands. We validate the interaction with nectin-1 through orthogonal assays. The study demonstrates the power of ProP-PD as a complementary approach to uncover interactions of potential biological relevance.
31.	Geironson Ulfsson, Linda, et al. (författare) Stability of peptide-HLA-I complexes and tapasin folding facilitation - tools to define immunogenic peptides 2012 Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 586:9, s. 1336-1343 Tidskriftsartikel (refereegranskat)abstract Only a small fraction of the peptides generated inside the cell end up being presented by HLA-I on the cell surface. High stability of peptide-HLA-I complexes and a low HLA-I tapasin-facilitation have been proposed to predict immunogenicity. We here set out to investigate if these parameters correlated and defined immunogenic peptides. Both peptide-HLA-B08:01 and peptide-HLA-A02:01 complexes showed small differences in tapasin-facilitation and larger differences in stability. This suggests that the stability of immunogenic peptide-HLA-I complexes vary above an HLA-I allomorph dependent lower limit (e. g. > 2 h for HLA-A02:01), immunogenicity predicted by tapasin-facilitation may be defined by an equally allomorph unique upper value (e. g. tapasin-facilitation <1.5 for HLA-A02:01), and variation above the stability-threshold does not directly reflect a variation in tapasin-facilitation. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
32.	Ghosh, Moumita, et al. (författare) Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages 2011 Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 585:4, s. 623-9 Tidskriftsartikel (refereegranskat)abstract Moderate lysosomal membrane permeabilization (LMP) is an important inducer of apoptosis. Macrophages are professional scavengers and are rich in hydrolytic enzymes and iron. In the present study, we found that LMP by lysosomotropic detergent MSDH resulted in early up-regulation of lysosomal cathepsins, oxidative stress and ferritin up-regulation, and cell death. Lysosomotropic base NH(4)Cl reduced the ferritin induction and oxidative stress in apoptotic cells induced by MSDH. Cysteine cathepsin inhibitors significantly protected cell death and oxidative stress, but had less effect on ferritin induction. We conclude that oxidative stress induced by lysosomal rupture causes ferritin induction with concomitant mitochondrial damage, which are the potential target for prevention of cellular oxidative stress and cell death induced by typical lysosomotropic substances in different disorders.
33.	Grankvist, N, et al. (författare) Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain 2013 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 587:23, s. 3869-3874 Tidskriftsartikel (refereegranskat)
34.	Guo, J, et al. (författare) Membrane topology and search for potential redox partners of colon cancer-specific cytochrome P450 2W1 2016 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 590:3, s. 330-339 Tidskriftsartikel (refereegranskat)
35.	Gustafsson, Robert, et al. (författare) Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX-type gene cluster 2017 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 591:22, s. 3781-3792 Tidskriftsartikel (refereegranskat)abstract Botulinum neurotoxins are highly toxic substances and are all encoded together with one of two alternative gene clusters, the HA or the OrfX gene cluster. Very little is known about the function and structure of the proteins encoded in the OrfX gene cluster, which in addition to the toxin contains five proteins (OrfX1, OrfX2, OrfX3, P47, and NTNH). We here present the structures of OrfX2 and P47, solved to 2.1 and 1.8 Å, respectively. We show that they belong to the TULIP protein superfamily, which are often involved in lipid binding. OrfX1 and OrfX2 were both found to bind phosphatidylinositol lipids.
36.	Gustavsson, Anna-Karin, 1986, et al. (författare) Heterogeneity of glycolytic oscillatory behaviour in individual yeast cells 2014 Ingår i: FEBS Letters. - : Wiley. - 0014-5793. ; 588:1, s. 3-7 Forskningsöversikt (refereegranskat)abstract There are many examples of oscillations in biological systems and one of the most investigated is glycolytic oscillations in yeast. These oscillations have been studied since the 1950s in dense, synchronized populations and in cell-free extracts, but it has for long been unknown whether a high cell density is a requirement for oscillations to be induced, or if individual cells can oscillate also in isolation without synchronization. Here we present an experimental method and a detailed kinetic model for studying glycolytic oscillations in individual, isolated yeast cells and compare them to previously reported studies of single-cell oscillations. The importance of single-cell studies of this phenomenon and relevant future research questions are also discussed.
37.	Heinen, C, et al. (författare) Mutant p62/SQSTM1 UBA domains linked to Paget's disease of bone differ in their abilities to function as stabilization signals 2010 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 584:8, s. 1585-1590 Tidskriftsartikel (refereegranskat)
38.	Heldin, Carl-Henrik, et al. (författare) Regulation of EMT by TGFβ in cancer 2012 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 586:14, s. 1959-1970 Forskningsöversikt (refereegranskat)abstract Transforming growth factor-beta (TGF beta) suppresses tumor formation since it inhibits cell growth and promotes apoptosis. However, in advanced cancers TGF beta elicits tumor promoting effects through its ability to induce epithelial-mesenchymal transition (EMT) which enhances invasiveness and metastasis; in addition, TGF beta exerts tumor promoting effects on non-malignant cells of the tumor, including suppression of immune surveillance and stimulation of angiogenesis. TGF beta promotes EMT by transcriptional and posttranscriptional regulation of a group of transcription factors that suppresses epithelial features, such as expression of components of cell junctions and polarity complexes, and enhances mesenchymal features, such as production of matrix molecules and several cytokines and growth factors that stimulate cell migration. The EMT program has certain similarities with the stem cell program. Inducers and effectors of EMT are interesting targets for the development of improved diagnosis, prognosis and therapy of cancer.
39.	Hofvander, Per, et al. (författare) A prokaryotic acyl-CoA reductase performing reduction of fatty acyl-CoA to fatty alcohol 2011 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 585, s. 3538-3543 Annan publikation (refereegranskat)abstract The reduction of acyl-CoA or acyl-ACP to fatty alcohol occurs via a fatty aldehyde intermediate. In prokaryotes this reaction is thought to be performed by separate enzymes for each reduction step while in eukaryotes these reactions are performed by a single enzyme without the release of the intermediate fatty aldehyde. However, here we report that a purified fatty acyl reductase from Marinobacter aquaeolei VT8, evolutionarily related to the fatty acyl reductases in eukaryotes, catalysed both reduction steps. Thus, there are at least two pathways existing among prokaryotes for the reduction of activated acyl substrates to fatty alcohol. The Marinobacter fatty acyl reductase studied has a wide substrate range in comparison to what can be found among enzymes so far studied in eukaryotes. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
40.	Ingelsson, Björn, et al. (författare) Phosphoproteomics of Arabidopsis chloroplasts reveals involvement of the STN7 kinase in phosphorylation of nucleoid protein pTAC16 2012 Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 586:9, s. 1265-1271 Tidskriftsartikel (refereegranskat)abstract Light-regulated protein kinases STN7 and STN8 phosphorylate thylakoid membrane proteins and also affect expression of several chloroplast proteins via yet unknown mechanisms. Comparative phosphoproteomics of acetic acid protein extracts of chloroplasts from Arabidopsis thaliana wild type, stn7, stn8 and stn7stn8 mutants yielded two previously unknown findings: (i) neither STN7 nor STN8 kinase was required for phosphorylation of Ser-48 in Lhcb1.1–1.3 proteins; and (ii) phosphorylation of Thr-451 in pTAC16 protein was STN7-dependent. pTAC16 was found distributed between thylakoids and nucleoid. Its knockout did not affect the nucleoid protein composition and the Thr-451 phosphorylated protein was excluded from the nucleoid. Thr-451 of pTAC16 is conserved in all studied plants and its phosphorylation may regulate membrane-anchoring functions of the nucleoid.
41.	Ivarsson, Ylva (författare) Plasticity of PDZ domains in ligand recognition and signaling 2012 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 586:17, s. 2638-47 Tidskriftsartikel (refereegranskat)abstract The PDZ domain is a protein-protein interacting module that plays an important role in the organization of signaling complexes. The recognition of short intrinsically disordered C-terminal peptide motifs is the archetypical PDZ function, but the functional repertoire of this versatile module also includes recognition of internal peptide sequences, dimerization and phospholipid binding. The PDZ function can be tuned by various means such as allosteric effects, changes of physiological buffer conditions and phosphorylation of PDZ domains and/or ligands, which poses PDZ domains as dynamic regulators of cell signaling. This review is focused on the plasticity of the PDZ interactions.
42.	Jakubauskiene, Egle, et al. (författare) G/A polymorphism in intronic sequence affects the processing of MAO-B gene in patients with Parkinson disease 2012 Ingår i: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 586:20, s. 3698-3704 Tidskriftsartikel (refereegranskat)abstract Monoamine oxidase B (MAO-B) plays an important role in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. Increased levels of MAO-B mRNA and enzymatic activity have been reported in platelets from patients with Parkinsons and Alzheimers diseases, however the triggers of enhanced mRNA levels are unknown. Our results demonstrate for the first time that G/A dimorphism in intron 13 sequence creates splicing enhancer thus stimulating intron 13 removal efficiency. The increased MAO-B protein levels might serve as a surrogate marker for - Parkinson disease.
43.	Jakubauskiene, Egle, et al. (författare) G/A polymorphism in intronic sequence affects the processing of MAO-B gene in patients with Parkinson disease (vol 586, pg 3698, 2012) 2013 Ingår i: FEBS Letters. - : Elsevier. - 0014-5793. Annan publikation (refereegranskat)abstract n/a
44.	Josefsen, K, et al. (författare) AKAP 18 alpha and gamma have opposing effects on insulin release in INS-1E cells 2010 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 584:1, s. 81-85 Tidskriftsartikel (refereegranskat)
45.	Kahle, Maximilian, et al. (författare) Insights into the mechanism of nitric oxide reductase from a Fe-B-depleted variant 2019 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:12, s. 1351-1359 Tidskriftsartikel (refereegranskat)abstract A key step of denitrification, the reduction of toxic nitric oxide to nitrous oxide, is catalysed by cytochrome c-dependent NO reductase (cNOR). cNOR contains four redox-active cofactors: three hemes and a nonheme iron (Fe-B). Heme b(3) and Fe-B constitute the active site, but the specific mechanism of NO-binding events and reduction is under debate. Here, we used a recently constructed, fully folded and hemylated cNOR variant that lacks Fe-B to investigate the role of Fe-B during catalysis. We show that in the Fe-B-less cNOR, binding of both NO and O-2 to heme b(3) still occurs but further reduction is impaired, although to a lesser degree for O-2 than for NO. Implications for the catalytic mechanisms of cNOR are discussed.
46.	Kim, YM, et al. (författare) Impaired melanoma growth in VASP deficient mice 2011 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 585:15, s. 2533-2536 Tidskriftsartikel (refereegranskat)
47.	Klaubauf, Sylvia, 1981, et al. (författare) A novel L-arabinose-responsive regulator discovered in the rice-blast fungus Pyricularia oryzae (Magnaporthe oryzae) 2016 Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 590:4, s. 550-558 Tidskriftsartikel (refereegranskat)abstract In this study we identified the L-arabinose-responsive regulator of Pyricularia oryzae that regulates L-arabinose release and catabolism. Previously we identified the Zn2Cys6 transcription factor (TF), AraR, that has this role in the Trichocomaceae family (Eurotiales), but is absent in other fungi. Candidate Zn2Cys6 TF genes were selected according to their transcript profiles on L-arabinose. Deletion mutants of these genes were screened for their growth phenotype on L-arabinose. One mutant, named Delta ara1, was further analyzed. Our analysis demonstrated that Ara1 from P. oryzae is the functional analog of AraR from A. niger, while there is no significant sequence similarity between them.
48.	Košenina, Sara, et al. (författare) Crystal structure of the catalytic domain of the Weissella oryzae botulinum-like toxin 2019 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:12, s. 1403-1410 Tidskriftsartikel (refereegranskat)abstract Botulinum neurotoxins (BoNTs) are the most potent toxins known. So far, eight serotypes have been identified that all act as zinc-dependent endopeptidases targeting SNARE proteins and inhibiting the release of neurotransmitters. Recently, the first botulinum toxin-like protein was identified outside the Clostridial genus, designated BoNT/Wo in the genome of Weissella oryzae. Here, we report the 1.6 angstrom X-ray crystal structure of the light chain of BoNT/Wo (LC/Wo). LC/Wo presents the core fold common to BoNTs but has an unusually wide, open and negatively charged catalytic pocket, with an additional Ca2+ ion besides the zinc ion and a unique ss-hairpin motif. The structural information will help establish the substrate profile of BoNT/Wo and help our understanding of how BoNT evolved.
49.	Krishnaswamyreddy, Sumitha, et al. (författare) A β-mannan utilisation locus in Bacteroides ovatus involves a GH36 α-galactosidase active on galactomannans 2016 Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 590:14, s. 2106-2118 Tidskriftsartikel (refereegranskat)abstract The Bacova_02091 gene in the β-mannan utilisation locus of Bacteroides ovatus encodes a family GH36 α-galactosidase (BoGal36A), transcriptionally upregulated during growth on galactomannan. Characterisation of recombinant BoGal36A reveals unique properties compared to other GH36 α-galactosidases, which preferentially hydrolyse terminal α-galactose in raffinose family oligosaccharides. BoGal36A prefers hydrolysing internal galactose substitutions from intact and depolymerized galactomannan. BoGal36A efficiently releases (>90%) galactose from guar and locust bean galactomannans, resulting in precipitation of the polysaccharides. As compared to other GH36 structures, the BoGal36A 3D model displays a loop deletion, resulting in a wider active site cleft which likely can accommodate a galactose-substituted polymannose backbone. This article is protected by copyright. All rights reserved.
50.	Krishnaswamyreddy, Sumitha, et al. (författare) Phylogenetic analysis and substrate specificity of GH2 β-mannosidases from Aspergillus species. 2013 Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 587:21, s. 3444-3449 Tidskriftsartikel (refereegranskat)abstract Phylogenetic analysis of glycoside hydrolase family 2 including Aspergillus sequences and characterised β-mannosidases from other organisms, clusters putative Aspergillus β-mannosidases in two distinct clades (A and B). Aspergillus species have at least one paralog in each of the two clades. It appears that clade A members are extracellular and clade B members intracellular. Substrate specificity analysis of MndA of Aspergillus niger (clade A) and MndB of Aspergillus nidulans (clade B) show that MndB, in contrast to MndA, does not hydrolyse polymeric mannan and has probably evolved to hydrolyse small unbranched β-mannosides like mannobiose. A 3D-model of MndB provides further insight.

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