Reconciling the “old” and “new” views of protein allostery: A molecular simulation study of chemotaxis Y protein (CheY)

Publisher Website
Google Scholar
Abstract
A combination of thirty-two 10-ns-scale molecular dynamics simulations were used to explore the coupling between conformational transition and phosphorylation in the bacteria chemotaxis Y protein (CheY), as a simple but representative example of protein allostery. Results from these simulations support an activation mechanism in which the β4–α4 loop, at least partially, gates the isomerization of Tyr106. The roles of phosphorylation and the conserved Thr87 are deemed indirect in that they stabilize the active configuration of the β4–α4 loop. The indirect role of the activation event (phosphorylation) and/or conserved residues in stabilizing, rather than causing, specific conformational transition is likely a feature in many signaling systems. The current analysis of CheY also helps to make clear that neither the “old” (induced fit) nor the “new” (population shift) views for protein allostery are complete, because they emphasize the kinetic (mechanistic) and thermodynamic aspects of allosteric transitions, respectively. In this regard, an issue that warrants further analysis concerns the interplay of concerted collective motion and sequential local structural changes in modulating cooperativity between distant sites in biomolecules. Proteins 2006.