Dynamic Protein Interaction Networks and New Structural Paradigms in Signaling.

Autor: Csizmok V; Molecular Structure & Function, The Hospital for Sick Children , Toronto, ON M5G 0A4, Canada., Follis AV; Department of Structural Biology, St. Jude Children's Research Hospital , Memphis, Tennessee 38105, United States., Kriwacki RW; Department of Structural Biology, St. Jude Children's Research Hospital , Memphis, Tennessee 38105, United States.; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Sciences Center , Memphis, Tennessee 38163, United States., Forman-Kay JD; Molecular Structure & Function, The Hospital for Sick Children , Toronto, ON M5G 0A4, Canada.; Department of Biochemistry, University of Toronto , Toronto, ON M5S 1A8, Canada.
Jazyk: angličtina
Zdroj: Chemical reviews [Chem Rev] 2016 Jun 08; Vol. 116 (11), pp. 6424-62. Date of Electronic Publication: 2016 Feb 29.
DOI: 10.1021/acs.chemrev.5b00548
Abstrakt: Understanding signaling and other complex biological processes requires elucidating the critical roles of intrinsically disordered proteins (IDPs) and regions (IDRs), which represent ∼30% of the proteome and enable unique regulatory mechanisms. In this review, we describe the structural heterogeneity of disordered proteins that underpins these mechanisms and the latest progress in obtaining structural descriptions of conformational ensembles of disordered proteins that are needed for linking structure and dynamics to function. We describe the diverse interactions of IDPs that can have unusual characteristics such as "ultrasensitivity" and "regulated folding and unfolding". We also summarize the mounting data showing that large-scale assembly and protein phase separation occurs within a variety of signaling complexes and cellular structures. In addition, we discuss efforts to therapeutically target disordered proteins with small molecules. Overall, we interpret the remodeling of disordered state ensembles due to binding and post-translational modifications within an expanded framework for allostery that provides significant insights into how disordered proteins transmit biological information.
Databáze: MEDLINE
Externí odkaz: