Segmental motions, not a two-state concerted switch, underlie allostery in CheY

Structure. 2012 Aug 8;20(8):1363-73. doi: 10.1016/j.str.2012.05.008. Epub 2012 Jun 21.

Abstract

The switch between an inactive and active conformation is an important transition for signaling proteins, yet the mechanisms underlying such switches are not clearly understood. Escherichia coli CheY, a response regulator protein from the two-component signal transduction system that regulates bacterial chemotaxis, is an ideal protein for the study of allosteric mechanisms. By using 15N CPMG relaxation dispersion experiments, we monitored the inherent dynamic switching of unphosphorylated CheY. We show that CheY does not undergo a two-state concerted switch between the inactive and active conformations. Interestingly, partial saturation of Mg2+ enhances the intrinsic allosteric motions. Taken together with chemical shift perturbations, these data indicate that the μs-ms timescale motions underlying CheY allostery are segmental in nature. We propose an expanded allosteric network of residues, including W58, that undergo asynchronous, local switching between inactive and active-like conformations as the primary basis for the allosteric mechanism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Allosteric Regulation
  • Allosteric Site
  • Amino Acid Substitution
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Catalytic Domain
  • Escherichia coli*
  • Hydrogen Bonding
  • Magnesium / chemistry
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Methyl-Accepting Chemotaxis Proteins
  • Models, Molecular*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • Bacterial Proteins
  • Membrane Proteins
  • Methyl-Accepting Chemotaxis Proteins
  • cheY protein, E coli
  • Magnesium