Hall, BA;
Armitage, JP;
Sansom, MS;
(2011)
Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.
PLoS Computational Biology
, 7
(10)
, Article e1002204. 10.1371/journal.pcbi.1002204.
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Abstract
Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors.
| Type: | Article |
|---|---|
| Title: | Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling. |
| Location: | US |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pcbi.1002204 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pcbi.1002204 |
| Language: | English |
| Additional information: | © 2011 Hall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3197627 |
| Keywords: | Amino Acid Sequence, Escherichia coli, Escherichia coli Proteins, Membrane Proteins, Molecular Dynamics Simulation, Molecular Sequence Data, Mutation, Protein Structure, Secondary, Receptors, Cell Surface, Signal Transduction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1330462 |
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