Dynamically driven protein allostery

Nat Struct Mol Biol. 2006 Sep;13(9):831-8. doi: 10.1038/nsmb1132. Epub 2006 Aug 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Allosteric Regulation
  • Cyclic AMP / metabolism
  • Cyclic AMP Receptor Protein / chemistry*
  • Cyclic AMP Receptor Protein / metabolism
  • Entropy
  • Escherichia coli / metabolism
  • Models, Biological
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Subunits / chemistry

Substances

  • Cyclic AMP Receptor Protein
  • Protein Subunits
  • Cyclic AMP