How do disordered regions achieve comparable functions to structured domains?

Protein Sci. 2015 Jun;24(6):909-22. doi: 10.1002/pro.2674. Epub 2015 May 15.

Abstract

The traditional structure to function paradigm conceives of a protein's function as emerging from its structure. In recent years, it has been established that unstructured, intrinsically disordered regions (IDRs) in proteins are equally crucial elements for protein function, regulation and homeostasis. In this review, we provide a brief overview of how IDRs can perform similar functions to structured proteins, focusing especially on the formation of protein complexes and assemblies and the mediation of regulated conformational changes. In addition to highlighting instances of such functional equivalence, we explain how differences in the biological and physicochemical properties of IDRs allow them to expand the functional and regulatory repertoire of proteins. We also discuss studies that provide insights into how mutations within functional regions of IDRs can lead to human diseases.

Keywords: IDRs in protein complexes; disorder-to-order transitions; disordered proteins; macromolecular protein assemblies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Intrinsically Disordered Proteins* / chemistry
  • Intrinsically Disordered Proteins* / metabolism
  • Intrinsically Disordered Proteins* / physiology
  • Mice
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Tertiary*
  • Proteome

Substances

  • Intrinsically Disordered Proteins
  • Proteome