DOI: 10.7554/elife.08419. CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling

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

10.7554/elife.08419

Crossref journal-article

eLife Sciences Publications, Ltd

eLife (4374)

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.

Bibliography

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. CLOCKSS.

Authors 8

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

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Dates

Type	When
Created	9 years, 9 months ago (Nov. 19, 2015, 7:48 a.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 8:50 p.m.)
Indexed	1 month ago (July 30, 2025, 1:08 p.m.)
Issued	9 years, 9 months ago (Nov. 19, 2015)
Published	9 years, 9 months ago (Nov. 19, 2015)
Published Online	9 years, 9 months ago (Nov. 19, 2015)

Funders 7

National Institute of General Medical Sciences 10.13039/100000057
Region: Americas
gov (National government)
Labels2
1. U.S. National Institute of General Medical Sciences
2. NIGMS
Awards1
1. R01GM085043
National Science Foundation 10.13039/100000001
Region: Americas
gov (National government)
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1. U.S. National Science Foundation
2. NSF
3. US NSF
4. USA NSF
Awards1
1. PHY-1430124
National Institute of General Medical Sciences 10.13039/100000057
Region: Americas
gov (National government)
Labels2
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2. NIGMS
Awards1
1. P50GM082251-7518
National Institute of General Medical Sciences 10.13039/100000057
Region: Americas
gov (National government)
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Awards1
1. 9P41GM104601
National Institute of General Medical Sciences 10.13039/100000057
Region: Americas
gov (National government)
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Awards1
1. 5R01GM098243
National Science Foundation 10.13039/100000001
Region: Americas
gov (National government)
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2. NSF
3. US NSF
4. USA NSF
Awards1
1. OCI-0725070
National Science Foundation 10.13039/100000001
Region: Americas
gov (National government)
Labels4
1. U.S. National Science Foundation
2. NSF
3. US NSF
4. USA NSF
Awards1
1. ACI-1238993

BibTeX

@article{Cassidy_2015, title={CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling}, volume={4}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.08419}, DOI={10.7554/elife.08419}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Cassidy, C Keith and Himes, Benjamin A and Alvarez, Frances J and Ma, Jun and Zhao, Gongpu and Perilla, Juan R and Schulten, Klaus and Zhang, Peijun}, year={2015}, month=nov }

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