A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors

Nat Commun. 2013;4:2881. doi: 10.1038/ncomms3881.

Abstract

Bacterial chemoreceptors are widely used as a model system for elucidating the molecular mechanisms of transmembrane signalling and have provided a detailed understanding of how ligand binding by the receptor modulates the activity of its associated kinase CheA. However, the mechanisms by which conformational signals move between signalling elements within a receptor dimer and how they control kinase activity remain unknown. Here, using long molecular dynamics simulations, we show that the kinase-activating cytoplasmic tip of the chemoreceptor fluctuates between two stable conformations in a signal-dependent manner. A highly conserved residue, Phe396, appears to serve as the conformational switch, because flipping of the stacked aromatic rings of an interacting F396-F396' pair in the receptor homodimer takes place concomitantly with the signal-related conformational changes. We suggest that interacting aromatic residues, which are common stabilizers of protein tertiary structure, might serve as rotameric molecular switches in other biological processes as well.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Chemotaxis
  • Conserved Sequence
  • Dimerization
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Escherichia coli / physiology
  • Escherichia coli Proteins
  • Histidine Kinase
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Methyl-Accepting Chemotaxis Proteins
  • Molecular Sequence Data
  • Phenylalanine / chemistry*
  • Phenylalanine / genetics
  • Phenylalanine / metabolism
  • Protein Conformation

Substances

  • Bacterial Proteins
  • Escherichia coli Proteins
  • Membrane Proteins
  • Methyl-Accepting Chemotaxis Proteins
  • Phenylalanine
  • Histidine Kinase
  • cheA protein, E coli