Understanding the physical mechanisms by which signals are transduced across a lipid bilayer is central to an account of cell signalling. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors. 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. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity.
The simulations reveal a clear correlation between small (ca. 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. 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. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a 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. Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane.
0 kommentar(er)
