title: Insights into correlated motions and long-range interactions in CheY derived from molecular dynamics simulations.
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 Salmonella typhimurium and the CheY-BeF(3)(-) active mimic structure (with BeF(3)(-) removed) from Escherichia 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 Thr-87 or Ile-95 rotameric forms, are observed for the previously identified g+ and g- rotamer sampling by Tyr-106. These molecular dynamics 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.
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Knaggs
authors.forename: Freddie R
authors.initials: FR
authors.lastname: Salsbury
authors.forename: Marshall Hall
authors.initials: MH
authors.lastname: Edgell
authors.forename: Jacquelyn S
authors.initials: JS
authors.lastname: Fetrow
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D003198:Computer Simulation; D029968:Escherichia coli Proteins; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013223:Statistics as Topic; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; C000607606:cheY protein, E coli