DisProt 7.0: a major update of the database of disordered proteins

Piovesan, Damiano; Tabaro, Francesco; Mičetić, Ivan; Necci, Marco; Quaglia, Federica; Oldfield, Christopher J.; Aspromonte, Maria Cristina; Davey, Norman E.; Davidović, Radoslav; Dosztányi, Zsuzsanna; Elofsson, Arne; Gasparini, Alessandra; Hatos, András; Kajava, Andrey V.; Kalmár, Lajos; Leonardi, Emanuela; Lázár, Tamás; Macedo-Ribeiro, Sandra; Macossay-Castillo, Mauricio; Mészáros, Attila; Minervini, Giovanni; Murvai, Nikoletta; Pujols, Jordi; Roche, Daniel B.; Salladini, Edoardo; Schád, Éva; Schramm, Antoine; Szabó, Beáta; Tantos, Ágnes; Tonello, Fiorella; Tsirigos, Konstantinos D.; Veljković, Nevena; Ventura, Salvador; Vranken, Wim; Warholm, Per; Uversky, Vladimir N.; Dunker, A. Keith; Longhi, Sonia; Tompa, Péter; Tosatto, Silvio C. E.

doi:10.1093/nar/gkw1056

Cited by 271 publications

(260 citation statements)

References 37 publications

(42 reference statements)

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“…The 119 proteins corresponding to DisProt entries satisfying this criterion (15% of DisProt entries; see LBID.xml database in Supporting Information) are referred to as “LBIDPs” throughout the manuscript. LBID.xml database includes DisProt and UniProt identifiers, protein name, source organism, length of amino acid sequence and its fraction corresponding to IDPRs, positions of IDPRs, molecular functions of IDPRs according to DisProt, list of PDB entries for IDPRs, structural domains and motifs according to PROSITE, list of available ligands, PDB entries for lipid–protein complexes, and amino acid composition of the lipid‐binding sites. Manual analysis of LBIDPs for presence of literature sources confirming their lipid‐binding properties gave 88 proteins (74% of LBIDPs and 11% of DisProt entries).…”

Section: Resultsmentioning

confidence: 99%

“…The data on lipid‐binding proteins were collected based on the database of IDPs DisProt 7 v 0.5 (11‐05‐2017) (https://www.disprot.org/) that contains 803 experimentally validated IDPs with 2167 IDPRs, https://www.disprot.org/ using Python 3.3 programming language (https://www.python.org/), as implemented in PyCharm v.3.0.2 development environment. Matplotlib Python plotting library and NumPy numerical mathematics extension were used.…”

Section: Methodsmentioning

confidence: 99%

“…Despite all these observations, the occurrence of lipid‐binding proteins among IDPs and structural consequences of lipid binding by IDPs/IDPRs have not been systematically studied as yet. To fill this gap, we have analyzed here the database of disordered proteins, DisProt (https://www.disprot.org/), to evaluate the prevalence of lipid‐binding IDPs (LBIDPs). Since lipid molecules are prone to self‐assembly into a variety of structures (bilayers, vesicles, etc.…”

Section: Introductionmentioning

confidence: 99%

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Does Intrinsic Disorder in Proteins Favor Their Interaction with Lipids?

et al. 2019

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Intrinsically disordered proteins (IDPs) are implicated in a range of human diseases, some of which are associated with the ability to bind to lipids. Although the presence of solvent‐exposed hydrophobic regions in IDPs should favor their interactions with low‐molecular‐weight hydrophobic/amphiphilic compounds, this hypothesis has not been systematically explored as of yet. In this study, the analysis of the DisProt database with regard to the presence of lipid‐binding IDPs (LBIDPs) reveals that they comprise, at least, 15% of DisProt entries. LBIDPs are classified into four groups by ligand type, functional categories, domain structure, and conformational state. 57% of LBIDPs are classified as ordered according to the CH‐CDF analysis, and 70% of LBIDPs possess lengths of disordered regions below 50%. To investigate the lipid‐binding properties of IDPs for which lipid binding is not reported, three proteins from different conformational groups are rationally selected. They all are shown to bind linoleic (LA) and oleic (OA) acids with capacities ranging from 9 to 34 LA/OA molecules per protein molecule. The association with LA/OA causes the formation of high‐molecular‐weight lipid–protein complexes. These findings suggest that lipid binding is common among IDPs, which can favor their involvement in lipid metabolism.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Does Intrinsic Disorder in Proteins Favor Their Interaction with Lipids?

et al. 2019

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“…201,093 matches were found. Since flexibility is known to be a pre-requisite for such modification to occur, the database of known intrinsically unstructured proteins [36] was also searched. A list of 101 candidate proteins was obtained, which is displayed in Supplementary Table 1.…”

Section: Resultsmentioning

confidence: 99%

Hotspots of age-related protein degradation: the importance of neighboring residues for the formation of non-disulfide crosslinks derived from cysteine

Friedrich

Wang

Oakley

et al. 2017

Biochemical Journal

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Over time, the long-lived proteins that are present throughout the human body deteriorate. Typically, they become racemised, truncated and covalently crosslinked. One reaction responsible for age-related protein crosslinking in the lens was elucidated recently and shown to involve spontaneous formation of dehydroalanine (DHA) intermediates from phosphoserine. Cys residues are another potential source of DHA, and evidence was found for this in a number of lens crystallins. In the human lens, some sites were more prone to forming non-disulfide covalent crosslinks than others. Foremost among them was Cys 5 in βA4 crystallin. The reason for this enhanced reactivity was investigated using peptides. Oxidation of Cys to cystine was a pre-requisite for DHA formation and DHA production was accelerated markedly by the presence of a Lys, one residue separated from Cys 5. Modelling and direct investigation of the N-terminal sequence of βA4 crystallin, as well as a variety of homologous peptides, showed that the epsilon amino group of Lys can promote DHA production by nucleophilic attack on the alpha proton of cystine. Once a DHA residue was generated, it could form inter-molecular crosslinks with Lys and Cys. In the lens, the most abundant crosslink involved Cys 5 of βA4 crystallin attached via a thioether bond to glutathione. These findings illustrate the potential of Cys and disulfide bonds to act as precursors for irreversible covalent crosslinks and the role of nearby amino acids in creating “hotpsots” for the spontaneous processes responsible for protein degradation in aged tissues.

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“…DisProt is the first curated database that contains a collection of experimentally verified IDPs and IDRs [6]. The latest release contains a total of 694 proteins with 1539 disordered regions (a just published newer release expands to more than 800 entries [7] and we will update ours in the next version). D2P2, on the other hand, consists of computationally predicted IDPs from 1765 proteomes from 1256 distinct species [8].…”

Section: Introductionmentioning

confidence: 99%

DisBind: A database of classified functional binding sites in disordered and structured regions of intrinsically disordered proteins

Dou

Sha

et al. 2017

BMC Bioinformatics

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BackgroundIntrinsically unstructured or disordered proteins function via interacting with other molecules. Annotation of these binding sites is the first step for mapping functional impact of genetic variants in coding regions of human and other genomes, considering that a significant portion of eukaryotic genomes code for intrinsically disordered regions in proteins.ResultsDisBind (available at http://biophy.dzu.edu.cn/DisBind) is a collection of experimentally supported binding sites in intrinsically disordered proteins and proteins with both structured and disordered regions. There are a total of 226 IDPs with functional site annotations. These IDPs contain 465 structured regions (ORs) and 428 IDRs according to annotation by DisProt. The database contains a total of 4232 binding residues (from UniProt and PDB structures) in which 2836 residues are in ORs and 1396 in IDRs. These binding sites are classified according to their interacting partners including proteins, RNA, DNA, metal ions and others with 2984, 258, 383, 350, and 262 annotated binding sites, respectively. Each entry contains site-specific annotations (structured regions, intrinsically disordered regions, and functional binding regions) that are experimentally supported according to PDB structures or annotations from UniProt.ConclusionThe searchable DisBind provides a reliable data resource for functional classification of intrinsically disordered proteins at the residue level.

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DisProt 7.0: a major update of the database of disordered proteins

Cited by 271 publications

References 37 publications

Does Intrinsic Disorder in Proteins Favor Their Interaction with Lipids?

Does Intrinsic Disorder in Proteins Favor Their Interaction with Lipids?

Hotspots of age-related protein degradation: the importance of neighboring residues for the formation of non-disulfide crosslinks derived from cysteine

DisBind: A database of classified functional binding sites in disordered and structured regions of intrinsically disordered proteins

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