Allostery is a fundamental process by which distant sites within a protein system sense each other. Allosteric regulation is such an efficient mechanism that it is used to control protein activity in most biological processes, including signal transduction, metabolism, catalysis, and gene regulation. Over recent years, our view and understanding of the fundamental principles underlying allostery have been enriched and often utterly reshaped. This has been especially so for powerful techniques such as nuclear magnetic resonance spectroscopy, which offers an atomic view of the intrinsic motions of proteins. Here, I discuss recent results on the catabolite activator protein (CAP) that have drastically revised our view about how allosteric interactions are modulated. CAP has provided the first experimentally identified system showing that (i) allostery can be mediated through changes in protein motions, in the absence of changes in the mean structure of the protein, and (ii) favorable changes in protein motions may activate allosteric proteins that are otherwise structurally inactive.
© 2012 New York Academy of Sciences.