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1.	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.
2.	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.
3.	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.
4.	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.
5.	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.
6.	Palmer, Nathan, et al. (författare) Diverse roles for CDK-associated activity during spermatogenesis 2019 Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 593:20, s. 2925-2949 Forskningsöversikt (refereegranskat)abstract The primary function of cyclin-dependent kinases (CDKs) in complex with their activating cyclin partners, is to promote mitotic division in somatic cells. This canonical cell cycle-associated activity is also crucial for fertility as it allows the proliferation and differentiation of stem cells within the reproductive organs to generate meiotically competent cells. Intriguingly several CDKs exhibit meiosis-specific functions and are essential for the completion of the two reductional meiotic divisions required to generate haploid gametes. These meiosis-specific functions are mediated by both known CDK/cyclin complexes and meiosis-specific CDK-regulators and are important for a variety of processes during meiotic prophase. The majority of meiotic defects observed upon deletion of these proteins occur during the extended prophase I of the first meiotic division. Importantly a lack of redundancy is seen within the meiotic arrest phenotypes described for many of these proteins suggesting intricate layers of cell cycle control are required for normal meiotic progression. Using the process of male germ cell development (spermatogenesis) as a reference, this review seeks to highlight the diverse roles of selected CDKs their activators, and their regulators during gametogenesis.
7.	Scaletti, Emma, et al. (författare) Structural basis of inhibition of the human serine hydroxymethyltransferase SHMT2 by antifolate drugs 2019 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 593:14, s. 1863-1873 Tidskriftsartikel (refereegranskat)abstract Serine hydroxymethyltransferase (SHMT) is the major source of 1-carbon units required for nucleotide synthesis. Humans have cytosolic (SHMT1) and mitochondrial (SHMT2) isoforms, which are upregulated in numerous cancers, making the enzyme an attractive drug target. Here, we show that the antifolates lometrexol and pemetrexed are inhibitors of SHMT2 and solve the first SHMT2-antifolate structures. The antifolates display large differences in their hydrogen bond networks despite their similarity. Lometrexol was found to be the best hSHMT1/2 inhibitor from a panel antifolates. Comparison of apo hSHMT1 with antifolate bound hSHMT2 indicates a highly conserved active site architecture. This structural information offers insights as to how these compounds could be improved to produce more potent and specific inhibitors of this emerging anti-cancer drug target.
8.	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.
9.	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.
10.	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.
11.	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.
12.	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.
13.	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.
14.	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.
15.	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)
16.	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.
17.	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.
18.	Liu, Jingyi, et al. (författare) Giardia intestinalis cystatin is a potent inhibitor of papain, parasite cysteine proteases and, to a lesser extent, human cathepsin B 2019 Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 593:12, s. 1313-1325 Tidskriftsartikel (refereegranskat)abstract Cystatins are important regulators of papain-like cysteine proteases. In the protozoan parasite Giardia intestinalis, papain-like cysteine proteases play an essential role in the parasite's biology and pathogenicity. Here, we characterized a cysteine protease inhibitor of G. intestinalis that belongs to type-I-cystatins. The parasite cystatin is shown to be a strong inhibitor of papain (K-i approximate to 0.3 nm) and three parasite cysteine proteases (CP14019, CP16160 and CP16779, K-i approximate to 0.9-5.8 nm), but a weaker inhibitor of human cathepsin B (K-i approximate to 79.9 nm). The protein localizes mainly in the cytoplasm. Together, these data suggest that cystatin of G. intestinalis plays a role in the regulation of cysteine protease activities in the parasite and, possibly, in the interaction with the host.
19.	Lundin, Camilla Rydström, et al. (författare) Modulation of O-2 reduction in Saccharomyces cerevisiae mitochondria 2017 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 591:24, s. 4049-4055 Tidskriftsartikel (refereegranskat)abstract Respiratory supercomplex factor (Rcf) 1 is a membrane-bound protein that modulates the activity of cytochrome c oxidase (CytcO) in Saccharomycescerevisiae mitochondria. To investigate this regulatory mechanism, we studied the interactions of CytcO with potassium cyanide (KCN) upon removal of Rcf Delta. While the addition of KCN to the wild-type mitochondria results in a full reduction of heme a, with the rcf Delta mitochondria, a significant fraction remains oxidized. Upon addition of ascorbate in the presence of O-2 and KCN, the reduction level of hemes a and b was a factor of similar to 2 larger with the wild-type than with the rcf Delta mitochondria. These data indicate that turnover of CytcO was less blocked in rcf Delta than in the wild-type mitochondria, suggesting that Rcf Delta modulates the structure of the catalytic site.
20.	Marino, Jacopo, et al. (författare) Small protein domains fold inside the ribosome exit tunnel 2016 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 590:5, s. 655-660 Tidskriftsartikel (refereegranskat)abstract Cotranslational folding of small protein domains within the ribosome exit tunnel may be an important cellular strategy to avoid protein misfolding. However, the pathway of cotranslational folding has so far been described only for a few proteins, and therefore, it is unclear whether folding in the ribosome exit tunnel is a common feature for small protein domains. Here, we have analyzed nine small protein domains and determined at which point during translation their folding generates sufficient force on the nascent chain to release translational arrest by the SecM arrest peptide, both in vitro and in live E. coli cells. We find that all nine protein domains initiate folding while still located well within the ribosome exit tunnel.
21.	Martinez Molledo, M, et al. (författare) Tripeptide binding in a proton-dependent oligopeptide transporter 2018 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 592:19, s. 3239-3247 Tidskriftsartikel (refereegranskat)
22.	Mutz, CN, et al. (författare) EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway 2016 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 590:14, s. 2063-2075 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
23.	North, Rachel A, et al. (författare) Structure and inhibition of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus 2016 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 590:23, s. 4414-4428 Tidskriftsartikel (refereegranskat)abstract N-Acetylneuraminate lyase is the first committed enzyme in the degradation of sialic acid by bacterial pathogens. In this study, we analyzed the kinetic parameters of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus (MRSA). We determined that the enzyme has a relatively high KM of 3.2 mm, suggesting that flux through the catabolic pathway is likely to be controlled by this enzyme. Our data indicate that sialic acid alditol, a known inhibitor of N-acetylneuraminate lyase enzymes, is a stronger inhibitor of MRSA N-acetylneuraminate lyase than of Clostridium perfringens N-acetylneuraminate lyase. Our analysis of the crystal structure of ligand-free and 2R-sialic acid alditol-bound MRSA N-acetylneuraminate lyase suggests that subtle dynamic differences in solution and/or altered binding interactions within the active site may account for species-specific inhibition.
24.	Otte, J, et al. (författare) New insights into human primordial germ cells and early embryonic development from single-cell analysis 2017 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 591:15, s. 2226-2240 Tidskriftsartikel (refereegranskat)
25.	Ren, XY, et al. (författare) Characterization of mammalian glutaredoxin isoforms as S-denitrosylases 2019 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 593:14, s. 1799-1806 Tidskriftsartikel (refereegranskat)
26.	Sharma, Satyan, et al. (författare) The fusion pore, 60 years after the first cartoon 2018 Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 592:21, s. 3542-3562 Tidskriftsartikel (refereegranskat)
27.	Stolp, B, et al. (författare) Microbial pathogenesis revealed by intravital microscopy: pros, cons and cautions 2016 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 590:13, s. 2014-2026 Tidskriftsartikel (refereegranskat)
28.	Treuter, E, et al. (författare) Transcriptional repression in macrophages-basic mechanisms and alterations in metabolic inflammatory diseases 2017 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 591:19, s. 2959-2977 Tidskriftsartikel (refereegranskat)
29.	Wanrooij, Paulina H., et al. (författare) Ribonucleotides in mitochondrial DNA 2019 Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 593:13, s. 1554-1565 Forskningsöversikt (refereegranskat)abstract The incorporation of ribonucleotides (rNMPs) into DNA during genome replication has gained substantial attention in recent years and has been shown to be a significant source of genomic instability. Studies in yeast and mammals have shown that the two genomes, the nuclear DNA (nDNA) and the mitochondrial DNA (mtDNA), differ with regard to their rNMP content. This is largely due to differences in rNMP repair - whereas rNMPs are efficiently removed from the nuclear genome, mitochondria lack robust mechanisms for removal of single rNMPs incorporated during DNA replication. In this minireview, we describe the processes that determine the frequency of rNMPs in the mitochondrial genome and summarise recent findings regarding the effect of incorporated rNMPs on mtDNA stability and function.
30.	Zabeo, Davide, 1992, et al. (författare) Axonemal doublet microtubules can split into two complete singlets in human sperm flagellum tips. 2019 Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 593:9, s. 892-902 Tidskriftsartikel (refereegranskat)abstract Motile flagella are crucial for human fertility and embryonic development. The distal tip of the flagellum is where growth and intra-flagellar transport are coordinated. In most model organisms, but not all, the distal tip includes a 'singlet region', where axonemal doublet microtubules (dMT) terminate and only complete A-tubules extend as singlet microtubules (sMT) to the tip. How a human flagellar tip is structured is unknown. Here, the flagellar tip structure of human spermatozoa was investigated by cryo-electron tomography, revealing the formation of a complete sMT from both the A-tubule and B-tubule of dMTs. This different tip arrangement in human spermatozoa shows the need to investigate human flagella directly in order to understand their role in health and disease.
31.	Zare, Aman, et al. (författare) The gut microbiome participates in transgenerational inheritance of low temperature responses in Drosophila melanogaster 2018 Ingår i: FEBS Letters. - : John Wiley & Sons. - 0014-5793 .- 1873-3468. ; 592:24, s. 4078-4086 Tidskriftsartikel (refereegranskat)abstract Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germ-line although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome. This article is protected by copyright. All rights reserved.
32.	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.
33.	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)
34.	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.
35.	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.
36.	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.
37.	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.
38.	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.
39.	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)
40.	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.
41.	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.
42.	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.
43.	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]).
44.	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.
45.	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)
46.	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.
47.	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)
48.	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.
49.	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.
50.	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)

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