FuzDB: database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein complexes and higher-order assemblies.

Marton Miskei,Monika Fuxreiter,Csaba Antal

doi:10.1093/nar/gkw1019

Abstract

FuzDB (http://protdyn-database.org) compiles experimentally observed fuzzy protein complexes, where intrinsic disorder (ID) is maintained upon interacting with a partner (protein, nucleic acid or small molecule) and directly impacts biological function. Entries in the database have both (i) structural evidence demonstrating the structural multiplicity or dynamic disorder of the ID region(s) in the partner bound form of the protein and (ii) in vitro or in vivo biological evidence that indicates the significance of the fuzzy region(s) in the formation, function or regulation of the assembly. Unlike the other intrinsically disordered or unfolded protein databases, FuzDB focuses on ID regions within a biological context, including higher-order assemblies and presents a detailed analysis of the structural and functional data. FuzDB also provides interpretation of experimental results to elucidate the molecular mechanisms by which fuzzy regions—classified on the basis of topology and mechanism—interfere with the structural ensembles and activity of protein assemblies. Regulatory sites generated by alternative splicing (AS) or post-translational modifications (PTMs) are also collected. By assembling all this information, FuzDB could be utilized to develop stochastic structure–function relationships for proteins and could contribute to the emergence of a new paradigm.

Highlights

Disordered proteins (IDPs) or protein regions (IDRs) are abundant in eukaryotic organisms and are known to serve versatile biological roles [1,2]
A common assumption is that while intrinsic disorder (ID) proteins/regions have excessive conformational freedom in their free state in solution, this becomes rather limited when they interact with their partners [4]
Development of modern spectroscopic techniques (e.g. NMR, FRET, single molecule approaches) [7] and ensemble characterization methods [8,9] enabled researchers to obtain deeper, higher-resolution views of dynamic regions in protein complexes. These studies demonstrated that structural multiplicity or dynamic disorder could contribute to the formation, function or regulation of the assembly, a phenomenon referred as fuzziness [10,11]

Summary

Introduction

Disordered proteins (IDPs) or protein regions (IDRs) are abundant in eukaryotic organisms and are known to serve versatile biological roles [1,2]. The minimum information required for consideration as a database entry is the following: the name of the protein and its partner(s), and either the structural or the functional data indicating the fuzziness of the assembly. The minimum information needed for a public FuzDB entry is the following: the name of the protein and its partner, cross-reference to Uniprot, protein function, both structural and functional data supporting fuzziness, detection method, annotation and classification of the fuzzy region, significance of fuzziness and key reference(s).

Results

Conclusion