Structure of the constitutively active double mutant CheYD13K Y106W alone and in complex with a FliM peptide

J Mol Biol. 2004 Sep 24;342(4):1325-35. doi: 10.1016/j.jmb.2004.07.084.

Abstract

CheY is a member of the response regulator protein superfamily that controls the chemotactic swimming response of motile bacteria. The CheY double mutant D13K Y106W (CheY**) is resistant to phosphorylation, yet is a highly effective mimic of phosphorylated CheY in vivo and in vitro. The conformational attributes of this protein that enable it to signal in a phosphorylation-independent manner are unknown. We have solved the crystal structure of selenomethionine-substituted CheY** in the presence of its target, a peptide (FliM16) derived from the flagellar motor switch, FliM, to 1.5A resolution with an R-factor of 19.6%. The asymmetric unit contains four CheY** molecules, two with FliM16 bound, and two without. The two CheY** molecules in the asymmetric unit that are bound to FliM16 adopt a conformation similar to BeF3- -activated wild-type CheY, and also bind FliM16 in a nearly identical manner. The CheY** molecules that do not bind FliM16 are found in a conformation similar to unphosphorylated wild-type CheY, suggesting that the active phenotype of this mutant is enabled by a facile interconversion between the active and inactive conformations. Finally, we propose a ligand-binding model for CheY and CheY**, in which Ile95 changes conformation in a Tyr/Trp106-dependent manner to accommodate FliM.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Methyl-Accepting Chemotaxis Proteins
  • Models, Molecular
  • Mutation*
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Signal Transduction
  • Tyrosine / metabolism

Substances

  • Bacterial Proteins
  • Membrane Proteins
  • Methyl-Accepting Chemotaxis Proteins
  • FliM protein, Bacteria
  • Tyrosine

Associated data

  • PDB/1U8T