Intrinsically Disordered Proteins: An Overview

Abstract

Many proteins and protein segments cannot attain a single stable three-dimensional structure under physiological conditions; instead, they adopt multiple interconverting conformational states. Such intrinsically disordered proteins or protein segments are highly abundant across proteomes, and are involved in various effector functions. This review focuses on different aspects of disordered proteins and disordered protein regions, which form the basis of the so-called "Disorder-function paradigm" of proteins. Additionally, various experimental approaches and computational tools used for characterizing disordered regions in proteins are discussed. Finally, the role of disordered proteins in diseases and their utility as potential drug targets are explored.

Keywords: intrinsically disordered proteins; intrinsically disordered regions; protein function; protein structure.

Figure 1

The two paradigms of protein structure and function. According to the well-established ‘structure–function paradigm’, a three-dimensional native structure under physiological conditions is vital for a protein to perform its biological function (for example, enzyme-catalyzed reactions). The more recent ‘disorder–function paradigm’ states that a protein can carry out its biological function without attaining a 3-D stable folded structure under physiological conditions (for example, protein binding to other cellular molecules). For representative purpose, residues coding for ordered/globular domains are shown in ‘green’ color, and residues coding for disordered proteins/segments are shown in ‘red’. At the proteome level, the structured domains and intrinsically disordered regions (IDRs) are two functional building blocks of proteins.

Figure 2

Functional aspects of IDPs/IDRs. Intrinsically disordered proteins/regions’ functional classes and elements are described here. The functional class scheme describes eight different categories into which IDPs/IDRs can be grouped based on their biological function. The different functional classes include Entropic chains, Modification sites, Disordered chaperones, Molecular effectors, Molecular recognition assemblers, Molecular recognition scavengers, Metal sponges, and Unknown. IDPs/IDRs’ functions are mediated mainly through three types of structural elements, namely Short Linear Motifs (SLiMs), Molecular Recognition Features (MORFs), and Intrinsically Disordered Domains (IDDS).