The ensemble nature of allostery

• Published in: Nature (London) Vol. 508; no. 7496; pp. 331 - 339
• Main Authors: Motlagh, Hesam N., Wrabl, James O., Li, Jing, Hilser, Vincent J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.04.2014; Nature Publishing Group
• Subjects: 631/45; 631/57; Allosteric proteins; Allosteric Regulation; Allosteric Site; Binding sites; Biological research; Biology; Biology, Experimental; Chemical properties; Cooperative binding (Biochemistry); Hemoglobins - chemistry; Hemoglobins - metabolism; Humanities and Social Sciences; Ligands; Models, Molecular; multidisciplinary; Protein Unfolding; Proteins; Proteins - chemistry; Proteins - metabolism; review-article; Science; Structure; Thermodynamics; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13001

Allostery is the process by which biological macromolecules transmit the effect of binding at one site to another, often distal, functional site, allowing for the regulation of activity; here facilitation of allostery through dynamic and intrinsically disordered proteins is discussed, and a framework to unify the description of allosteric mechanisms for different systems is proposed. The changing shape of allostery The classic model for understanding allostery, the regulated process by which biological macromolecules (typically enzymes) transmit the effect of binding at one site to another with subsequent change in activity, has focused on unique structures and the structural changes observed between different functional forms. During the past 20 years there has been a realization that allostery is associated with changes in dynamics as well. In this Review, Vincent Hilser and colleagues discuss how allostery can be facilitated by dynamic and intrinsically disordered proteins and propose a framework to unify the description of allosteric mechanisms from different systems. Allostery is the process by which biological macromolecules (mostly proteins) transmit the effect of binding at one site to another, often distal, functional site, allowing for regulation of activity. Recent experimental observations demonstrating that allostery can be facilitated by dynamic and intrinsically disordered proteins have resulted in a new paradigm for understanding allosteric mechanisms, which focuses on the conformational ensemble and the statistical nature of the interactions responsible for the transmission of information. Analysis of allosteric ensembles reveals a rich spectrum of regulatory strategies, as well as a framework to unify the description of allosteric mechanisms from different systems.