Insights into Correlated Motion and Long-range Interactions in CheY Derived from Molecular Dynamics Simulations

¹ Wake Forest University
² UNC-Chapel Hill

^* To whom correspondence should be addressed. E-mail: fetrowjs{at}wfu.edu.

Submitted on January 26, 2006
Revised on March 13, 2006
Accepted on 10 November 2006

	Abstract

CheY is a response regulator protein involved in bacterial chemotaxis. Much is known about its active and inactive conformations, but little is known about the mechanisms underlying long-range interactions or correlated motions. To investigate these events, molecular dynamics simulations were performed on the unphosphorylated, inactive structure from S. typhimurium and the CheY-BeF₃^- active mimic structure (with BeF₃^- removed) from E. coli. Simulations utilized both sequences in each conformation to discriminate sequence- and structure-specific behavior. The previously identified conformational differences between the inactive and active conformations of the strand-4-helix-4 loop, which are present in these simulations, arise from the structural, and not the sequence, differences. The simulations identify previously unreported structure-specific flexibility features in this loop and sequence-specific flexibility features in other regions of the protein. Both structure- and sequence-specific long-range interactions are observed in the active and inactive ensembles. In the inactive ensemble, two distinct mechanisms based on Thr87 or Ile95 rotameric forms, are observed for the previously identified g+ and g- rotamer sampling by Tyr106. These MD simulations have thus identified both sequence- and structure-specific differences in flexibility, long-range interactions, and rotameric form of key residues. Potential biological consequences of differential flexibility and long-range correlated motion are discussed.

Key Words: Tyr 106 rotamer, active/inactive conformation, allostery, bacterial chemotaxis, correlated motion, signal transduction