| 1. |
- Shu, Nanjiang, 1981-
(författare)
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Prediction of zinc-binding sites in proteins and efficient protein structure description and comparison
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A large number of proteins require certain metals to stabilize their structures or to function properly. About one third of all proteins in the Protein Data Bank (PDB) contain metals and it is estimated that approximately the same proportion of all proteins are metalloproteins. Zinc, the second most abundant transition metal found in eukaryotic organisms, plays key roles, mainly structural and catalytic, in many biological functions. Predicting whether a protein binds zinc and even the accurate location of binding sites is important when investigating the function of an experimentally uncharacterized protein. Describing and comparing protein structures with both efficiency and accuracy are essential for systematic annotation of functional properties of proteins, be it on an individual or on a genome scale. Dozens of structure comparison methods have been developed in the past decades. In recent years, several research groups have endeavoured in developing methods for fast comparison of protein structures by representing the three-dimensional (3D) protein structures as one-dimensional (1D) geometrical strings based on the shape symbols of clustered regions of φ/ψ torsion angle pairs of the polypeptide backbones. These 1D geometrical strings, shape strings, are as compact as 1D secondary structures but carry more elaborate structural information in loop regions and thus are more suitable for fast structure database searching, classification of loop regions and evaluation of model structures. In this thesis, a new method for predicting zinc-binding sites in proteins from amino acid sequences is described. This method predicts zinc-binding Cys, His, Asp and Glu (the four most common zinc-binding residues) with 75% precision (86% for Cys and His only) at 50% recall according to a solid 5-fold cross-validation on a non-redundant set of the PDB chains containing 2727 unique chains, of which 235 bind to zinc. This method predicts zinc-binding Cys and His with about 10% higher precision at different recall levels compared to a previously published method. In addition, different methods for describing and comparing protein structures are reviewed. Some recently developed methods based on 1D geometrical representation of backbone structures are emphasized and analyzed in details.
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| 2. |
- Hennerdal, Aron, et al.
(författare)
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Internal duplications in alpha-helical membrane protein topologies are common but the nonduplicated forms are rare
- 2010
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2305-2318
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Tidskriftsartikel (refereegranskat)abstract
- Many alpha-helical membrane proteins contain internal symmetries, indicating that they might have evolved through a gene duplication and fusion event Here, we have characterized internal duplications among membrane proteins of known structure and in three complete genomes We found that the majority of large transmembrane (TM) proteins contain an internal duplication The duplications found showed a large variability both in the number of TM-segments included and in their orientation Surprisingly, an approximately equal number of antiparallel duplications and parallel duplications were found However, of all 11 superfamilies with an internal duplication, only for one, the AcrB Multidrug Efflux Pump, the duplicated unit could be found in its nonduplicated form An evolutionary analysis of the AcrB homologs indicates that several independent fusions have occurred, including the fusion of the SecD and SecF proteins into the 12-TM-protein SecDF in Brucella and Staphylococcus aureus In one additional case, the Vitamin B-12 transporter-like ABC transporters, the protein had undergone an additional fusion to form protein with 20 TM-helices in several bacterial genomes Finally, homologs to all human membrane proteins were used to detect the presence of duplicated and nonduplicated proteins This confirmed that only in rare cases can homologs with different duplication status be found, although internal symmetry is frequent among these proteins One possible explanation is that it is frequent that duplication and fusion events happen simultaneously and that there is almost always a strong selective advantage for the fused form
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| 3. |
- Cheung, Henry Lok Shan, et al.
(författare)
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Denitrification, anammox, and DNRA in oligotrophic continental shelf sediments
- 2024
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Ingår i: Limnology and Oceanography. - 1939-5590 .- 0024-3590.
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Tidskriftsartikel (refereegranskat)abstract
- Continental shelf sediments are considered hotspots for nitrogen (N) removal. While most investigations have quantified denitrification in shelves receiving large amounts of anthropogenic nutrient supply, we lack insight into the key drivers of N removal on oligotrophic shelves. Here, we measured rates of N removal through denitrification and anammox by the revised-isotope pairing technique (r-IPT) along the Northeastern New Zealand shelf. Denitrification dominated total N2 production at depths between 30 and 128 m with average rates (± SE) ranging from 65 ± 28 to 284 ± 72 μmol N m−2 d−1. N2 production by anammox ranged from 3 ± 1 to 28 ± 11 μmol N m−2 d−1 and accounted for 2–19% of total N2 production. DNRA was negligible in these oligotrophic settings. Parallel microbial community analysis showed that both Proteobacteria and Planctomycetota were key taxa driving denitrification. Denitrification displayed a negative correlation with oxygen penetration depth, and a positive correlation with macrofauna abundance. Our denitrification rates were comparable to oligotrophic shelves from the Arctic, but were lower than those from nutrient-rich Pacific and Atlantic shelves. Based on our results and existing IPT measurements, the global shelf denitrification rate was reassessed to be 53.5 ± 8.1 Tg N yr−1, equivalent to 20 ± 2% of marine N removal. We suggest that previous estimates of global shelf N loss might have been overestimated due to sampling bias toward areas with high N loads in the Northern Hemisphere.
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| 4. |
- Zhou, Tuping, et al.
(författare)
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A Novel Method for Accurate One-dimensional Protein Structure Prediction Based on Fragment Matching
- 2010
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 26:4, s. 470-477
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: The precise prediction of one-dimensional (1D) protein structure as represented by the protein secondary structure and 1D string of discrete state of dihedral angles (i.e. Shape Strings) is a prerequisite for the successful prediction of three-dimensional (3D) structure as well as protein-protein interaction. We have developed a novel 1D structure prediction method, called Frag1D, based on a straightforward fragment matching algorithm and demonstrated its success in the prediction of three sets of 1D structural alphabets, i.e. the classical three-state secondary structure, three-state Shape Strings and eight-state Shape Strings. Results: By exploiting the vast protein sequence and protein structure data available, we have brought secondary structure prediction closer to the expected theoretical limit. When tested by a leave-one-out cross validation on a non-redundant set of PDB cutting at 30% sequence identity containing 5860 protein chains, the overall per-residue accuracy for secondary structure prediction, i.e. Q3 is 82.9%. The overall per-residue accuracy for three-state and eight-state Shape Strings are 85.1% and 71.5% respectively. We have also benchmarked our program with the latest version of PSIPRED for secondary structure prediction and our program predicted 0.3% better in Q3 when tested on 2241 chains with the same training set. For Shape Strings, we compared our method with a recently published method with the same dataset and definition as used by that method. Our program predicted at 2.2% better in accuracy for three-state Shape Strings. By quantitatively investigating the effect of data base size on 1D structure prediction we show that the accuracy increases by about 1% with every doubling of the database size.
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| 5. |
- Svedäng, Henrik, et al.
(författare)
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Compensatory Feeding in Eastern Baltic Cod (Gadus morhua) : Recent Shifts in Otolith Growth and Nitrogen Content Suggest Unprecedented Metabolic Changes
- 2020
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Ingår i: Frontiers in Marine Science. - : FRONTIERS MEDIA SA. - 2296-7745. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The productivity of the Eastern Baltic cod (EBC) has been severely reduced over the last 25 years, for reasons that remain unclear. The size distribution of EBC has become increasingly truncated, condition and health status have deteriorated, and sexual maturation has started to occur at increasingly smaller sizes. Despite an increasing trend in recruitment during this period, reduced growth or increased mortality rates after the recruitment phase have resulted in decreasing landing levels and low profitability in the cod fishery, whereas the scientific community has difficulties in disentangling the causes of the decline of EBC. We studied changes in metabolic status in EBC between the capture years of 1995 and 2015, by investigating two aspects of fish metabolism that can be extracted retrospectively from otolith (earstone) morphometry and nitrogen content. Changes in relative otolith size to fish size are related to the metabolic history of the individual fish, and the otolith nitrogen content reveals the level of protein synthesis and feeding rate. Because otoliths accrue continuously on their surface and are biological stable (inert), the chemical content of the otolith trajectory reflects the timeline of the fish. We measured the N/Ca ratio as a proxy for protein content in EBC otolith along distal radius traverses from the core to the edge of the otolith by using secondary ion mass spectrometry (SIMS). Here we show that the otoliths have become smaller at a given fish size, and the ratio of N/Ca has increased over the studied period. These proxies reveal significant metabolic changes during the same period as the condition, and stock productivity has declined. We discuss potential mechanisms behind the metabolic changes, including elevated temperature and compensatory feeding due to nutrient deficiencies. Such changes in food quality may, in turn, relate to still unrecognized but on-going ecosystem shifts, where climate change could be the ultimate driver.
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| 6. |
- Johansson, Renzo, et al.
(författare)
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Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones
- 2016
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 24:6, s. 906-917
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides. Their overall activity is stimulated by ATP and downregulated by dATP via a genetically mobile ATP cone domain mediating the formation of oligomeric complexes with varying quaternary structures. The crystal structure and solution X-ray scattering data of a novel dATP-induced homotetramer of the Pseudomonas aeruginosa class I RNR reveal the structural bases for its unique properties, namely one ATP cone that binds two dATP molecules and a second one that is non-functional, binding no nucleotides. Mutations in the observed tetramer interface ablate oligomerization and dATP-induced inhibition but not the ability to bind dATP. Sequence analysis shows that the novel type of ATP cone may be widespread in RNRs. The present study supports a scenario in which diverse mechanisms for allosteric activity regulation are gained and lost through acquisition and evolutionary erosion of different types of ATP cone.
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| 7. |
- Allison, Timothy M., et al.
(författare)
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Complementing machine learning‐based structure predictions with native mass spectrometry
- 2022
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Ingår i: Protein Science. - : John Wiley & Sons. - 0961-8368 .- 1469-896X. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- The advent of machine learning-based structure prediction algorithms such as AlphaFold2 (AF2) and RoseTTa Fold have moved the generation of accurate structural models for the entire cellular protein machinery into the reach of the scientific community. However, structure predictions of protein complexes are based on user-provided input and may require experimental validation. Mass spectrometry (MS) is a versatile, time-effective tool that provides information on post-translational modifications, ligand interactions, conformational changes, and higher-order oligomerization. Using three protein systems, we show that native MS experiments can uncover structural features of ligand interactions, homology models, and point mutations that are undetectable by AF2 alone. We conclude that machine learning can be complemented with MS to yield more accurate structural models on a small and large scale.
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| 8. |
- Ismail, Nurzian, et al.
(författare)
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Charge-driven dynamics of nascent-chain movement through the SecYEG translocon
- 2015
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 22:2, s. 145-149
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Tidskriftsartikel (refereegranskat)abstract
- On average, every fifth residue in secretory proteins carries either a positive or a negative charge. In a bacterium such as Escherichia coli, charged residues are exposed to an electric field as they transit through the inner membrane, and this should generate a fluctuating electric force on a translocating nascent chain. Here, we have used translational arrest peptides as in vivo force sensors to measure this electric force during cotranslational chain translocation through the SecYEG translocon. We find that charged residues experience a biphasic electric force as they move across the membrane, including an early component with a maximum when they are 47-49 residues away from the ribosomal P site, followed by a more slowly varying component. The early component is generated by the transmembrane electric potential, whereas the second may reflect interactions between charged residues and the periplasmic membrane surface.
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| 9. |
- Capo, Eric, et al.
(författare)
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Oxygen-deficient water zones in the Baltic Sea promote uncharacterized Hg methylating microorganisms in underlying sediments
- 2022
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Ingår i: Limnology and Oceanography. - : Wiley. - 1939-5590 .- 0024-3590. ; 67:1, s. 135-146
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Tidskriftsartikel (refereegranskat)abstract
- Human-induced expansion of oxygen-deficient zones can have dramatic impacts on marine systems and its resident biota. One example is the formation of the potent neurotoxic methylmercury (MeHg) that is mediated by microbial methylation of inorganic divalent Hg (HgII) under oxygen-deficient conditions. A negative consequence of the expansion of oxygen-deficient zones could be an increase in MeHg production due to shifts in microbial communities in favor of microorganisms methylating Hg. There is, however, limited knowledge about Hg-methylating microbes, i.e., those carrying hgc genes critical for mediating the process, from marine sediments. Here, we aim to study the presence of hgc genes and transcripts in metagenomes and metatranscriptomes from four surface sediments with contrasting concentrations of oxygen and sulfide in the Baltic Sea. We show that potential Hg methylators differed among sediments depending on redox conditions. Sediments with an oxygenated surface featured hgc-like genes and transcripts predominantly associated with uncultured Desulfobacterota (OalgD group) and Desulfobacterales (including Desulfobacula sp.) while sediments with a hypoxic-anoxic surface included hgc-carrying Verrucomicrobia, unclassified Desulfobacterales, Desulfatiglandales, and uncharacterized microbes. Our data suggest that the expansion of oxygen-deficient zones in marine systems may lead to a compositional change of Hg-methylating microbial groups in the sediments, where Hg methylators whose metabolism and biology have not yet been characterized will be promoted and expand.
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| 10. |
- Vajda, Vivi, et al.
(författare)
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Geochemical Fingerprints of Ginkgoales Across the Triassic-Jurassic Boundary of Greenland
- 2021
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Ingår i: International journal of plant sciences. - Chicago : University of Chicago Press. - 1058-5893 .- 1537-5315. ; 182:7, s. 649-662
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Tidskriftsartikel (refereegranskat)abstract
- Premise of research. Geochemical fingerprinting of fossil plants is a relatively new research field complementing morphological analyses and providing information for paleoenvironmental interpretations. Ginkgoales contains a single extant species but was diverse through the Mesozoic and is an excellent target for biochemical analyses.Methodology. Cuticles derived from fresh and fallen autumn leaves of extant Ginkgo biloba and seven fossil gink- goalean leaf taxa, one seed fern taxon, and two taxa with bennettitalean affinity were analyzed by infrared (IR) microspec- troscopy at the D7 beamline in the MAX IV synchrotron laboratory, Sweden. The fossil material derives from Triassic and Jurassic successions of Greenland. Spectral data sets were compared and evaluated by hierarchical cluster analysis (HCA) and principal component analysis performed on vector-normalized, first-derivative IR absorption spectra.Pivotal results. The IR absorption spectra of the fossil leaves all reveal signatures that clearly indicate the pres- ence of organic compounds. Spectra of the extant G. biloba leaves reveal the presence of aliphatic chains, aromatic and ester carbonyl functional groups from polymer cutin and other waxy compounds, and polysaccharides. Inter- estingly, both the extant autumn leaves and the fossil specimens reveal the presence of carboxyl/ketone molecules, suggesting that chemical alterations during the initial stages of decomposition are preserved through fossilization. Two major subclusters were identified through HCA of the fossil spectra.Conclusions. Consistent chemical IR signatures, specific for each fossil taxon are present in cuticles, and suf- ficient molecular content is preserved in key regions to reflect the plants’ original chemical signatures. The alter- ations of the organic compounds are initiated as soon as the leaves are shed, with loss of proteins and increased ester and carboxyl/ketone compound production in the fallen leaves. We further show that the groupings of taxa reflect a combination of phylogeny and environmental conditions related to the end-Triassic event.
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