Disordered Proteins

Abstract

Intrinsically disordered proteins (IDPs) and disordered protein regions (IDPRs) do not have a specific three‐dimensional (3D) structure in their unbound states under physiological conditions, existing instead as dynamic structural ensembles. There are also subtler categories of disorder, such as conditional (or dormant) disorder and partial disorder. Both the ability of a protein/region to fold and the predisposition to stay intrinsically disordered are encoded in the amino acid sequence. Structurally, IDPs/IDPRs are characterised by high spatiotemporal heterogeneity. It is important to remember, however, that although structure and disorder are often treated as binary states, they actually sit on a structural continuum. Functionally, IDPs/IDPRs are often characterised by the ability to multitask and be promiscuous binders. The field of unstructural biology has arisen to explain proteins that fall outside of the classical structure–function paradigm. A major goal in the coming years will be to understand sequence‐to‐function relationships for disordered proteins. Key Concepts Many biologically important protein regions fail to form specific three‐dimensional (3D) structures in their unbound states under physiological conditions. Amino acid sequences of these intrinsically disordered proteins (IDPs) are noticeably different from sequences of ordered proteins and reliable predictors can be developed to distinguish the tendency of a protein to be structured or disordered. IDPs are highly abundant in nature and have numerous functions that complement the functional repertoire of ordered proteins. IDPs are characterised by high structural heterogeneity, and there is a structural continuum, with highly ordered proteins on one end and highly disordered proteins on the other. IDPs/IDPRs are commonly found in various human diseases where they often play crucial roles in pathogenesis. IDPs are crucial constituents of various membraneless organelles abundantly found in the cytoplasm and nucleoplasm of eukaryotic cells.