TY - JOUR
T1 - Structure and dynamics of the E. coli chemotaxis core signaling complex by cryo-electron tomography and molecular simulations
AU - Cassidy, C. Keith
AU - Himes, Benjamin A.
AU - Sun, Dapeng
AU - Ma, Jun
AU - Zhao, Gongpu
AU - Parkinson, John S.
AU - Stansfeld, Phillip J.
AU - Luthey-Schulten, Zaida
AU - Zhang, Peijun
N1 - Funding Information:
We thank Dr. Robin Corey for critical reading of the manuscript and many valuable suggestions, Professor Mark Sansom for fruitful discussions, and D. Bevan for computer technical support. This work was supported by the National Institutes of Health NIGMS Grants R01GM085043 (P.Z.), RO5GM19559 (J.S.P.) and P41GM104601 (Z.L.-S.), the US National Science Foundation grant PHY1430124 (Z.L.-S.), the UK Wellcome Trust Investigator Award 206422/Z/17/Z (P.Z.), the UK Biotechnology and Biological Sciences Research Council grants BB/S003339/1 (C.K.C., P.J.S., and P.Z.), BB/P01948X/1 and BB/ R002517/1 (P.J.S.), the Medical Research Council grant MR/S009213/1 (P.J.S), and the UK Wellcome Trust Technology Award 208361/Z/17/Z (P.J.S.). MD simulations were performed on the Blue Waters supercomputer, which is supported by the National Science Foundation (OCI-0725070 and ACI-1238993) and the state of Illinois. This work is part of the Petascale Computational Resource Grant (ACI-1713784).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - To enable the processing of chemical gradients, chemotactic bacteria possess large arrays of transmembrane chemoreceptors, the histidine kinase CheA, and the adaptor protein CheW, organized as coupled core-signaling units (CSU). Despite decades of study, important questions surrounding the molecular mechanisms of sensory signal transduction remain unresolved, owing especially to the lack of a high-resolution CSU structure. Here, we use cryo-electron tomography and sub-tomogram averaging to determine a structure of the Escherichia coli CSU at sub-nanometer resolution. Based on our experimental data, we use molecular simulations to construct an atomistic model of the CSU, enabling a detailed characterization of CheA conformational dynamics in its native structural context. We identify multiple, distinct conformations of the critical P4 domain as well as asymmetries in the localization of the P3 bundle, offering several novel insights into the CheA signaling mechanism.
AB - To enable the processing of chemical gradients, chemotactic bacteria possess large arrays of transmembrane chemoreceptors, the histidine kinase CheA, and the adaptor protein CheW, organized as coupled core-signaling units (CSU). Despite decades of study, important questions surrounding the molecular mechanisms of sensory signal transduction remain unresolved, owing especially to the lack of a high-resolution CSU structure. Here, we use cryo-electron tomography and sub-tomogram averaging to determine a structure of the Escherichia coli CSU at sub-nanometer resolution. Based on our experimental data, we use molecular simulations to construct an atomistic model of the CSU, enabling a detailed characterization of CheA conformational dynamics in its native structural context. We identify multiple, distinct conformations of the critical P4 domain as well as asymmetries in the localization of the P3 bundle, offering several novel insights into the CheA signaling mechanism.
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U2 - 10.1038/s42003-019-0748-0
DO - 10.1038/s42003-019-0748-0
M3 - Article
C2 - 31925330
AN - SCOPUS:85077691088
SN - 2399-3642
VL - 3
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 24
ER -