On the roles of intrinsically disordered proteins and regions in cell communication and signaling

Abstract

For proteins, the sequence → structure → function paradigm applies primarily to enzymes, transmembrane proteins, and signaling domains. This paradigm is not universal, but rather, in addition to structured proteins, intrinsically disordered proteins and regions (IDPs and IDRs) also carry out crucial biological functions. For these proteins, the sequence → IDP/IDR ensemble → function paradigm applies primarily to signaling and regulatory proteins and regions. Often, in order to carry out function, IDPs or IDRs cooperatively interact, either intra- or inter-molecularly, with structured proteins or other IDPs or intermolecularly with nucleic acids. In this IDP/IDR thematic collection published in Cell Communication and Signaling, thirteen articles are presented that describe IDP/IDR signaling molecules from a variety of organisms from humans to fruit flies and tardigrades ("water bears") and that describe how these proteins and regions contribute to the function and regulation of cell signaling. Collectively, these papers exhibit the diverse roles of disorder in responding to a wide range of signals as to orchestrate an array of organismal processes. They also show that disorder contributes to signaling in a broad spectrum of species, ranging from micro-organisms to plants and animals.

Keywords: Amino acid sequence; Disorder prediction; Intrinsically disordered proteins; Protein structure.

Fig. 1

The time-courses of the increase in the number of publications dealing with intrinsic disorder (green bars) and the number of papers citing those publications (green line). Data for these plot were retrieved from Web of Science on August 01, 2021 using the following search criteria: TOPIC: (intrinsically disordered) OR TOPIC: (natively unfolded) OR TOPIC: (intrinsically unstructured) OR TOPIC: (natively unstructured) OR TOPIC: (intrinsically unfolded protein*)