Nature Structural & Molecular Biology
- 13, 831 - 838 (2006)
Published online: 13 August 2006; | doi:10.1038/nsmb1132
Dynamically driven protein allosteryNataliya Popovych1, Shangjin Sun1, Richard H Ebright2 & Charalampos G Kalodimos11
Department of Chemistry, Rutgers University, Newark, New Jersey 07102, USA. 2
Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
Correspondence should be addressed to Charalampos G Kalodimos babis@andromeda.rutgers.edu Allosteric interactions are typically considered to proceed through a series of discrete changes in bonding interactions that alter the protein conformation. Here we show that allostery can be mediated exclusively by transmitted changes in protein motions. We have characterized the negatively cooperative binding of cAMP to the dimeric catabolite activator protein (CAP) at discrete conformational states. Binding of the first cAMP to one subunit of a CAP dimer has no effect on the conformation of the other subunit. The dynamics of the system, however, are modulated in a distinct way by the sequential ligand binding process, with the first cAMP partially enhancing and the second cAMP completely quenching protein motions. As a result, the second cAMP binding incurs a pronounced conformational entropic penalty that is entirely responsible for the observed cooperativity. The results provide strong support for the existence of purely dynamics-driven allostery.
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