Analyzing IDPs in Interactomes

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 2141; p. 895
• Main Author: Uversky, Vladimir N
• Format: Journal Article
• Language: English
• Published: United States 2020
• Subjects: alpha-Synuclein - chemistry; Databases, Protein; Humans; Intrinsically Disordered Proteins - chemistry; Protein Binding; Protein Conformation; Protein Interaction Mapping; Protein Processing, Post-Translational; Software; Structure-Activity Relationship; User-Computer Interface; Posttranslational modification; PPI network; IDP; Protein-protein interaction; Interactome; Protein function; Hub protein; Prediction; Intrinsically disordered protein; Molecular recognition feature
• ISSN: 1940-6029
• DOI: 10.1007/978-1-0716-0524-0_46

Intrinsically disordered proteins (IDPs) and regions (IDRs) are commonly found in all proteomes analyzed so far. These proteins/regions are subject to numerous posttranslational modifications (PTMs) and alternative splicing, are involved in a wide range of cellular functions, and often facilitate protein-protein interactions (PPIs). Some of these proteins contain molecular recognition features (MoRFs), which are IDRs that bind to partner proteins and undergo disorder-to-order transitions. Although many IDPs/IDRs can fold upon binding, a large fraction of these proteins are known to maintain significant amounts of disorder in their bound states. Being well-recognized interaction specialists, IDPs/IDRs can participate in one-to-many and many-to-one interactions, where one IDP/IDR binds to multiple partners potentially gaining very different structures in the bound state, or where multiple unrelated IDPs/IDRs bind to one partner. As a result, IDPs frequently serve as hubs (i.e., proteins with many links) in complex PPI networks. The goal of this chapter is to describe computational and bioinformatics tools that can be used to look at the disorder status of proteins within a given PPI network and also to gain some knowledge on the disorder-based functionality of the members of this network. To this end, description is provided for some of the use of UniProt and DisProt databases, several databases generating PPI networks (BioGRID, IntAct, DIP, MINT, HPRD, APID, KEGG, and STRING), Composition profiler, some tools for the per-residue disorder predictions (PONDR VLXT, PONDR VL3, PONDR VSL2, PONDR-FIT, and IUPred), binary disorder classifiers CH-plot and CDF-plot and their combined CH-CDF analysis, web-based tools for the visualization of disorder distribution in a query protein (D P and MobiDB), as well as some tools for evaluation disorder-based functionality of proteins (ANCHOR, MoRFpred, DEPP, and ModPred).