CaltechAUTHORS
  A Caltech Library Service

Interdimer zipping in the chemoreceptor signaling domain revealed by molecular dynamics simulations

Petukh, Marharyta G. and Ortega, Davi R. and Baudry, Jerome and Zhulin, Igor B. (2019) Interdimer zipping in the chemoreceptor signaling domain revealed by molecular dynamics simulations. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20190823-084121873

[img] PDF - Submitted Version
Creative Commons Attribution.

7Mb
[img] PDF (Supplementary Figures and Tables) - Supplemental Material
Creative Commons Attribution.

4Mb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20190823-084121873

Abstract

Chemoreceptors are principal components of the bacterial sensory system that modulates cellular motility. They detect changes in the environment and transmit information to CheA histidine kinase, which ultimately controls cellular flagellar motors. The prototypical Tsr chemoreceptor in E. coli is a homodimer containing two principal functional modules: (i) a periplasmic ligand-binding domain and (ii) a cytoplasmic signaling domain. Chemoreceptor dimers are arranged into a trimer of dimers at the tip of the signaling domain comprising a minimal physical unit essential for enhancing the CheA activity several hundredfold. Trimers of dimers are arranged into highly ordered hexagon arrays at the cell pole; however, the mechanism underlying the trimer-of-dimer and higher order array formation remains unclear. Furthermore, molecular mechanisms of signal transduction that are likely to involve inter-dimer interactions are not fully understood. Here we apply all-atom, microsecond-time scale molecular dynamics simulations of the Tsr trimer of dimers atomic model in order to obtain further insight into potential interactions within the chemoreceptor signaling unit. We show extensive interactions between homodimers at the hairpin tip of the signaling domain, where strong hydrophobic interactions maintain binding. A subsequent zipping of homodimers is facilitated by electrostatic interactions, in particular by polar solvation energy and salt bridges that stabilize the final compact structure, which extends beyond the kinase interacting subdomain. Our study provides evidence that interdimer interactions within the chemoreceptor signaling domain are more complex than previously thought.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/745117DOIDiscussion Paper
ORCID:
AuthorORCID
Petukh, Marharyta G.0000-0001-8473-5677
Ortega, Davi R.0000-0002-8344-2335
Zhulin, Igor B.0000-0002-6708-5323
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. bioRxiv preprint first posted online Aug. 22, 2019. Author Contributions: M.G.P. conceived the study, performed computations, analyzed and interpreted data, and wrote the manuscript. D.R.O. conceived the study, performed computations, helped data analysis and interpretation, and helped write the manuscript. J.B. advised data analysis and interpretation, and helped write the manuscript. I.B.Z. conceived the study, analyzed and interpreted data, and wrote the manuscript. We thank Keith Cassidy for discussions during the early stages of this study and Sandy Parkinson for discussions and critical reading of the manuscript. This work was supported in part by the National Institutes of Health grant R35GM131760 to I.B.Z. This research used resources of the Oak Ridge Leadership Computing Facility at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05-00OR22725.
Funders:
Funding AgencyGrant Number
NIHR35GM131760
Department of Energy (DOE)DE-AC05-00OR22725
Record Number:CaltechAUTHORS:20190823-084121873
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190823-084121873
Official Citation:Interdimer zipping in the chemoreceptor signaling domain revealed by molecular dynamics simulations. Marharyta G. Petukh, Davi R. Ortega, Jerome Baudry, Igor B. Zhulin. bioRxiv 745117; doi: https://doi.org/10.1101/745117
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98145
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Aug 2019 15:49
Last Modified:03 Oct 2019 21:38

Repository Staff Only: item control page