| 1. |
- Hatos, Andras, et al.
(författare)
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DisProt : intrinsic protein disorder annotation in 2020
- 2020
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
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Tidskriftsartikel (refereegranskat)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
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| 2. |
- Huang, Rick K., et al.
(författare)
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Conformational Switching in PolyGln Amyloid Fibrils Resulting from a Single Amino Acid Insertion
- 2014
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:10, s. 2134-2142
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Tidskriftsartikel (refereegranskat)abstract
- The established correlation between neurodegenerative disorders and intracerebral deposition of polyglutamine aggregates motivates attempts to better understand their fibrillar structure. We designed polyglutamines with a few lysines inserted to overcome the hindrance of extreme insolubility and two D-lysines to limit the lengths of β-strands. One is 33 amino acids long (PolyQKd-33) and the other has one fewer glutamine (PolyQKd-32). Both form well-dispersed fibrils suitable for analysis by electron microscopy. Electron diffraction confirmed cross-β structures in both fibrils. Remarkably, the deletion of just one glutamine residue from the middle of the peptide leads to substantially different amyloid structures. PolyQKd-32 fibrils are consistently 10–20% wider than PolyQKd-33, as measured by negative staining, cryo-electron microscopy, and scanning transmission electron microscopy. Scanning transmission electron microscopy analysis revealed that the PolyQKd-32 fibrils have 50% higher mass-per-length than PolyQKd-33. This distinction can be explained by a superpleated β-structure model for PolyQKd-33 and a model with two β-solenoid protofibrils for PolyQKd-32. These data provide evidence for β-arch-containing structures in polyglutamine fibrils and open future possibilities for structure-based drug design.
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| 3. |
- Monzon, Alexander Miguel, et al.
(författare)
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A STRP-ed definition of Structured Tandem Repeats in Proteins
- 2023
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Ingår i: Journal of Structural Biology. - 1047-8477 .- 1095-8657. ; 215:4
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Tidskriftsartikel (refereegranskat)abstract
- Tandem Repeat Proteins (TRPs) are a class of proteins with repetitive amino acid sequences that have been studied extensively for over two decades. Different features at the level of sequence, structure, function and evolution have been attributed to them by various authors. And yet many of its salient features appear only when looking at specific subclasses of protein tandem repeats. Here, we attempt to rationalize the existing knowledge on Tandem Repeat Proteins (TRPs) by pointing out several dichotomies. The emerging picture is more nuanced than generally assumed and allows us to draw some boundaries of what is not a proper TRP. We conclude with an operational definition of a specific subset, which we have denominated STRPs (Structural Tandem Repeat Proteins), which separates a subclass of tandem repeats with distinctive features from several other less well-defined types of repeats. We believe that this definition will help researchers in the field to better characterize the biological meaning of this large yet largely understudied group of proteins.
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| 4. |
- Piovesan, Damiano, et al.
(författare)
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DisProt 7.0 : a major update of the database of disordered proteins
- 2017
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:D1, s. d219-D227
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Tidskriftsartikel (refereegranskat)abstract
- The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as regions that are at least five consecutive residues without well-defined structure. We base our assessment of disorder strictly on experimental evidence, such as X-ray crystallography and nuclear magnetic resonance ( primary techniques) and a broad range of other experimental approaches (secondary techniques). Confident and ambiguous annotations are highlighted separately. DisProt 7.0 presents classified knowledge regarding the experimental characterization and functional annotations of IDPs/IDRs, and is intended to provide an invaluable resource for the research community for a better understanding structural disorder and for developing better computational tools for studying disordered proteins.
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| 5. |
- Sagit, Rauan, 1985-
(författare)
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Variation in length of proteins by repeats and disorder regions
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Protein-coding genes evolve together with their genome and acquire changes, some of which affect the length of their protein products. This explains why equivalent proteins from different species can exhibit length differences. Variation in length of proteins during evolution arguably presents a large number of possibilities for improvement and innovation of protein structure and function. In order to contribute to an increased understanding of this process, we have studied variation caused by tandem domain duplications and insertions or deletions of intrinsically disordered residues.The study of two proteins, Nebulin and Filamin, together with a broader study of long repeat proteins (>10 domain repeats), began by confirming that tandem domains evolve by internal duplications. Next, we show that vertebrate Nebulins evolved by duplications of a seven-domain unit, yet the most recent duplications utilized different gene parts as duplication units. However, Filamin exhibits a checkered duplication pattern, indicating that duplications were followed by similarity erosions that were hindered at particular domains due to the presence of equivalent binding motifs. For long repeat proteins, we found that human segmental duplications are over-represented in long repeat genes. Additionally, domains that have formed long repeats achieved this primarily by duplications of two or more domains at a time.The study of homologous protein pairs from the well-characterized eukaryotes nematode, fruit fly and several fungi, demonstrated a link between variation in length and variation in the number of intrinsically disordered residues. Next, insertions and deletions (indels) estimated from HMM-HMM pairwise alignments showed that disordered residues are clearly more frequent among indel than non-indel residues. Additionally, a study of raw length differences showed that more than half of the variation in fungi proteins is composed of disordered residues. Finally, a model of indels and their immediate surroundings suggested that disordered indels occur in already disordered regions rather than in ordered regions.
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