Conformational transitions of adenylate kinase: switching by cracking

J Mol Biol. 2007 Mar 9;366(5):1661-71. doi: 10.1016/j.jmb.2006.11.085. Epub 2006 Dec 5.

Abstract

Conformational heterogeneity in proteins is known to often be the key to their function. We present a coarse grained model to explore the interplay between protein structure, folding and function which is applicable to allosteric or non-allosteric proteins. We employ the model to study the detailed mechanism of the reversible conformational transition of Adenylate Kinase (AKE) between the open to the closed conformation, a reaction that is crucial to the protein's catalytic function. We directly observe high strain energy which appears to be correlated with localized unfolding during the functional transition. This work also demonstrates that competing native interactions from the open and closed form can account for the large conformational transitions in AKE. We further characterize the conformational transitions with a new measure Phi(Func), and demonstrate that local unfolding may be due, in part, to competing intra-protein interactions.

Publication types

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

MeSH terms

  • Adenylate Kinase / chemistry*
  • Escherichia coli / enzymology
  • Models, Molecular
  • Protein Conformation*
  • Protein Denaturation
  • Protein Folding
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • Stress, Mechanical
  • Thermodynamics

Substances

  • Proteins
  • Adenylate Kinase