FuzDB: a new phase in understanding fuzzy interactions

Hatos, András; Monzón, Alexander Miguel; Tosatto, Silvio C. E.; Piovesan, Damiano; Fuxreiter, Mónika

doi:10.1093/nar/gkab1060

Cited by 27 publications

(33 citation statements)

References 50 publications

(70 reference statements)

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“…Protein annotations (mainly for natural proteins) such as localization, Gene Ontology (GO) term and sequence (if not provided by literature) in LLPSDB v2.0 were obtained from UniProt/NCBI, while the rest of annotations were mining and curated from other related databases. The linkages of the related databases [such as DisProt ( Quaglia et al , 2021 ), OMIM ( Amberger et al , 2019 ), IDEAL ( Fukuchi et al , 2014 ), AmyPro ( Varadi et al , 2018 ), FuzDB ( Hatos et al , 2021 ), etc.] for each protein were updated with the newest versions.…”

Section: Methodsmentioning

confidence: 99%

LLPSDB v2.0: an updated database of proteins undergoing liquid–liquid phase separation in vitro

et al. 2022

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Summary Emerging evidences have suggested that liquid–liquid phase separation (LLPS) of proteins plays a vital role both in a wide range of biological processes and in related diseases. Whether a protein undergoes phase separation not only is determined by the chemical and physical properties of biomolecule themselves, but also is regulated by environmental conditions such as temperature, ionic strength, pH, as well as volume excluded by other macromolecules. A web accessible database LLPSDB was developed recently by our group, in which all the proteins involved in LLPS in vitro as well as corresponding experimental conditions were curated comprehensively from published literatures. With the rapid increase of investigations in biomolecular LLPS and growing popularity of LLPSDB, we updated the database, and developed a new version LLPSDB v2.0. In comparison of the previously released version, more than double contents of data are curated, and a new class “Ambiguous system” is added. In addition, the web interface is improved, such as that users can search the database by selecting option “phase separation status” alone or combined with other options. We anticipate that this updated database will serve as a more comprehensive and helpful resource for users. Availability and implementation LLPSDB v2.0 is freely available at: http://bio-comp.org.cn/llpsdbv2 Supplementary information Supplementary data are available at Bioinformatics online.

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Section: Methodsmentioning

confidence: 99%

LLPSDB v2.0: an updated database of proteins undergoing liquid–liquid phase separation in vitro

et al. 2022

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“…DisProt ( 41 ), the database for intrinsically disordered protein, reports interestingly on the nuts and bolts of curation, harnessing both professional and community biocurators in a manner supported by a refactored ontology and incentivised by the APICURON database ( 42 ). The FuzDB Update ( 43 ) reports on fuzzy interactions, i.e. those exhibiting context-dependent conformational heterogeneity, an interaction style particularly common where one or both partners are classified as intrinsically disordered.…”

Section: New and Updated Databasesmentioning

confidence: 99%

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Rigden

Fernández

2021

Nucleic Acids Research

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The 2022 Nucleic Acids Research Database Issue contains 185 papers, including 87 papers reporting on new databases and 85 updates from resources previously published in the Issue. Thirteen additional manuscripts provide updates on databases most recently published elsewhere. Seven new databases focus specifically on COVID-19 and SARS-CoV-2, including SCoV2-MD, the first of the Issue's Breakthrough Articles. Major nucleic acid databases reporting updates include MODOMICS, JASPAR and miRTarBase. The AlphaFold Protein Structure Database, described in the second Breakthrough Article, is the stand-out in the protein section, where the Human Proteoform Atlas and GproteinDb are other notable new arrivals. Updates from DisProt, FuzDB and ELM comprehensively cover disordered proteins. Under the metabolism and signalling section Reactome, ConsensusPathDB, HMDB and CAZy are major returning resources. In microbial and viral genomes taxonomy and systematics are well covered by LPSN, TYGS and GTDB. Genomics resources include Ensembl, Ensembl Genomes and UCSC Genome Browser. Major returning pharmacology resource names include the IUPHAR/BPS guide and the Therapeutic Target Database. New plant databases include PlantGSAD for gene lists and qPTMplants for post-translational modifications. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Our latest update to the NAR online Molecular Biology Database Collection brings the total number of entries to 1645. Following last year's major cleanup, we have updated 317 entries, listing 89 new resources and trimming 80 discontinued URLs. The current release is available at http://www.oxfordjournals.org/nar/database/c/.

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“…These datasets represented stoichiometric, specific complexes of condensate-driver proteins based on experimental evidence or predictions. Protein regions in these complexes may represent the region, which is critical for condensate-formation (for example GCN4 [ 21 ], see other examples in FuzDB, fuzdb.org [ 13 ]; Supplementary Materials Table S1 ). In most cases, however, the droplet-driving regions are not well-defined.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to high concentration, variable stoichiometry and conformational heterogeneity, which all present bottlenecks for high-resolution structural studies of biomolecular condensates, one also needs to consider the impact of a wide range of cellular factors [ 32 ]. Stoichiometric complexes of droplet-forming proteins are characterized at high resolution [ 13 ], which can provide insights into the intrinsic factors driving liquid–liquid phase separation.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing experimental evidence shows that proteins may sample a wide range of binding modes in their stoichiometric complexes, from ordering to disordering upon binding coupled to decrease or increase of conformational entropy [ 11 , 12 ]. Disordered binding modes observed in specific assemblies of both structured and disordered proteins are achieved via many different binding configurations, leading to conformational heterogeneity in the bound state ( Figure 1 ) [ 13 ]. Protein sequences capable of forming disordered interactions lack the local compositional bias for ordered binding, and this feature is, in particular, enriched in sequences of droplet-driving proteins [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates

2022

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Biomolecular condensates challenge the classical concepts of molecular recognition. The variable composition and heterogeneous conformations of liquid-like protein droplets are bottlenecks for high-resolution structural studies. To obtain atomistic insights into the organization of these assemblies, here we have characterized the conformational ensembles of specific disordered complexes, including those of droplet-driving proteins. First, we found that these specific complexes exhibit a high degree of conformational heterogeneity. Second, we found that residues forming contacts at the interface also sample many conformations. Third, we found that different patterns of contacting residues form the specific interface. In addition, we observed a wide range of sequence motifs mediating disordered interactions, including charged, hydrophobic and polar contacts. These results demonstrate that selective recognition can be realized by variable patterns of weakly defined interaction motifs in many different binding configurations. We propose that these principles also play roles in determining the selectivity of biomolecular condensates.

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FuzDB: a new phase in understanding fuzzy interactions

Cited by 27 publications

References 50 publications

LLPSDB v2.0: an updated database of proteins undergoing liquid–liquid phase separation in vitro

LLPSDB v2.0: an updated database of proteins undergoing liquid–liquid phase separation in vitro

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates

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