title: A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors.
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.
authors: Joint Institute for Computational Sciences, University of Tennessee - Oak Ridge National Laboratory, Oak Ridge, Tennessee 37861, USA.
authors: Davi R
authors: DR
authors: Ortega
authors: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
authors: Chen
authors: C
authors: Yang
authors: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
authors: Peter
authors: P
authors: Ames
authors: 1] Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996, USA [2] Center for Molecular Biophysics, University of Tennessee - Oak Ridge National Laboratory, Oak Ridge, Tennessee 37861, USA.
authors: Jerome
authors: J
authors: Baudry
authors: Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
authors: John S
authors: JS
authors: Parkinson
authors: 1] Joint Institute for Computational Sciences, University of Tennessee - Oak Ridge National Laboratory, Oak Ridge, Tennessee 37861, USA [2] Department of Microbiology, University of Tennessee, Knoxville, Tennessee, 37996, USA [3] Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37861, USA.
authors: Igor B
authors: IB
authors: Zhulin
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D017124:Conserved Sequence; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029968:Escherichia coli Proteins; D000071677:Histidine Kinase; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D010649:Phenylalanine; D000071677:Histidine Kinase; C000607608:cheA protein, E coli