CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling

C. Keith Cassidy, Benjamin A. Himes, Frances J. Alvarez, Jun Ma, Gongpu Zhao, Juan R. Perilla, Klaus Schulten, Peijun Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Chemotactic responses in bacteria require large, highly ordered arrays of sensory proteins to mediate the signal transduction that ultimately controls cell motility. A mechanistic understanding of the molecular events underlying signaling, however, has been hampered by the lack of a high-resolution structural description of the extended array. Here, we report a novel reconstitution of the array, involving the receptor signaling domain, histidine kinase CheA, and adaptor protein CheW, as well as a density map of the core-signaling unit at 11.3 Å resolution, obtained by cryo-electron tomography and sub-tomogram averaging. Extracting key structural constraints from our density map, we computationally construct and refine an atomic model of the core array structure, exposing novel interfaces between the component proteins. Using all-atom molecular dynamics simulations, we further reveal a distinctive conformational change in CheA. Mutagenesis and chemical cross-linking experiments confirm the importance of the conformational dynamics of CheA for chemotactic function.

Original languageEnglish (US)
Article numbere08419
JournaleLife
Volume4
Issue numberNOVEMBER2015
DOIs
StatePublished - Nov 19 2015

ASJC Scopus subject areas

  • General Neuroscience
  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology

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