How do disordered regions achieve comparable functions to structured domains?
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.
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom.
Natasha S
NS
Latysheva
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom.
Tilman
T
Flock
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom.
Robert J
RJ
Weatheritt
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom.
Sreenivas
S
Chavali
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom.
M Madan
MM
Babu
D000818:Animals; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020543:Proteome
D064267:Intrinsically Disordered Proteins; D020543:Proteome
IDRs in protein complexes; disorder-to-order transitions; disordered proteins; macromolecular protein assemblies