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Cassidy CK, Himes BA, Alvarez FJ, et al. CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling. Elife. 2015;4doi: 10.7554/eLife.08419.
Cassidy, C. K., Himes, B. A., Alvarez, F. J., Ma, J., Zhao, G., Perilla, J. R., Schulten, K., & Zhang, P. (2015). CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling. eLife, 4. https://doi.org/10.7554/eLife.08419
Cassidy, C Keith, et al. "CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling." eLife vol. 4 (2015). doi: https://doi.org/10.7554/eLife.08419
Cassidy CK, Himes BA, Alvarez FJ, Ma J, Zhao G, Perilla JR, Schulten K, Zhang P. CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling. Elife. 2015 Nov 19;4. doi: 10.7554/eLife.08419. PMID: 26583751; PMCID: PMC6746300.
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Elife. 2015 Nov 19;4. doi: 10.7554/eLife.08419.

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

eLife

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

Affiliations

  1. Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, United States.
  2. Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.

PMID: 26583751 PMCID: PMC6746300 DOI: 10.7554/eLife.08419

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.

Keywords: E. coli; biophysics; computational biology; structural biology; systems biology

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