The multifaceted roles of intrinsic disorder in protein complexes

Abstract

Edited by Wilhelm Just Keywords:Intrinsically disordered protein Intrinsically disordered protein region Protein-protein interaction Protein complex Scaffold Regulation Polyvalent interaction a b s t r a c t Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are important constituents of many protein complexes, playing various structural, functional, and regulatory roles. In such disorder-based protein complexes, functional disorder is used both internally (for assembly, movement, and functional regulation of the different parts of a given complex) and externally (for interactions of a complex with its external regulators). In complex assembly, IDPs/IDPRs serve as the molecular glue that cements complexes or as highly flexible scaffolds. Disorder defines the order of complex assembly and the ability of a protein to be involved in polyvalent interactions. It is at the heart of various binding mechanisms and interaction modes ascribed to IDPs. Disorder in protein complexes is related to multifarious applications of induced folding and induced functional unfolding, or defines the entropic chain activities, such as stochastic machines and binding rheostats. This review opens a FEBS Letters Special Issue on Dynamics, Flexibility, and Intrinsic Disorder in protein assemblies and represents a brief overview of intricate roles played by IDPs and IDPRs in various aspects of protein complexes.

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

“…As it follows from the aforementioned observations, intrinsic disorder plays a number of important roles in organization, maintenance, and control of protein complexes (37). It has also been emphasized that protein complexes utilize two different types of functional disorder: internal, i.e.…”

“…There are at least two different interaction modes that define the formation of such polyvalent complexes, namely semi-static and dynamic (37). One of the illustrative examples of such interactions is given by IDP/IDPR wrapping around the binding partner, which produces a polyvalent complex, where several disjoint ordered segments of an IDP/IDPR bind to disjoint and spatially distant binding sites on the surface of an ordered partner (38).…”

Toward increased concentration sensitivity for continuous wave EPR investigations of spin-labeled biological macromolecules at high fields

“…For instance, CW spectra at W-and D-bands provide an enhanced capability to detect sub-nanosecond correlation times [43]. This is particularly suitable for studying IDPs, in which the time scale normally falls into the 0.1 to 2 ns region [37,38,[44][45][46][47][48][69][70][71][72].…”

“…IDPs are described as proteins or protein segments that lack a well-defined secondary or tertiary structure [44][45][46][47][48].…”

Disrupted in schizophrenia 1 (DISC1) is a constituent of the mammalian mitochondrial contact site and cristae organizing system (MICOS) complex, and is essential for oxidative phosphorylation

“…Intrinsically disordered proteins (IDP) are depleted in hydrophobic residues that usually drive protein folding, and are enriched in charged and polar residues (34), as is the case for the 60% out of the 350 amino acids that form DISC1 N-terminal domain (14). IDPs are important constituents of protein complexes, playing crucial roles in assembly, as the molecular stick that strengthens complexes or as highly flexible scaffolds that mediate interactions with other complexes (35). This suggests that the association of DISC1 to the IMM is mediated by its binding to another MICOS subunit.…”