PhosIDP: a web tool to visualize the location of phosphorylation sites in disordered regions

Sonia T Nicolaou,Owen J Jonathan,Chandra S Verma,Jim Warwicker,Max Hebditch

doi:10.1038/s41598-021-88992-0

Abstract

Charge is a key determinant of intrinsically disordered protein (IDP) and intrinsically disordered region (IDR) properties. IDPs and IDRs are enriched in sites of phosphorylation, which alters charge. Visualizing the degree to which phosphorylation modulates the charge profile of a sequence would assist in the functional interpretation of IDPs and IDRs. PhosIDP is a web tool that shows variation of charge and fold propensity upon phosphorylation. In combination with the displayed location of protein domains, the information provided by the web tool can lead to functional inferences for the consequences of phosphorylation. IDRs are components of many proteins that form biological condensates. It is shown that IDR charge, and its modulation by phosphorylation, is more tightly controlled for proteins that are essential for condensate formation than for those present in condensates but inessential.

Highlights

Charge is a key determinant of intrinsically disordered protein (IDP) and intrinsically disordered region (IDR) properties
Previous work has demonstrated the importance of net charge and the balance between positive and negative charge in the analysis of IDR conformation and function[26]
The crucial role that phosphorylation plays in many systems, through sitespecific interactions, and with global switching of charge profiles, can be quickly and conveniently studied with phosIDP, subject to data collation in the UniProt database

Summary

Introduction

Charge is a key determinant of intrinsically disordered protein (IDP) and intrinsically disordered region (IDR) properties. Disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins have been challenging the traditional structure–function paradigm over the last two decades They exhibit a range of conformations, from molten globules to random coils[1], with their net charge correlated to their conformational preference[2,3]. Conformational ensembles of IDPs/IDRs depend on the balance of all charge interactions in the protein, rather than individual short-range interactions between the binding site of the protein and a binding partner. They can interact with partners through several distinct binding motifs and/or conformations, and various functional elements will switch between availability for interaction and burial[10]. Offline calculations for datasets of proteins are presented that demonstrate the role of phosphorylation in modulating charge for IDRs in core LLPS proteins, but not client proteins

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