Mechanosensitive Closed-Closed Transitions in Large Membrane Proteins: Osmoprotection and Tension Damping

摘要: Multiconformation membrane proteins are mechanosensitive (MS) if their conformations displace different bilayer areas. Might MS closed-closed transitions serve as tension buffers, that is, “spandex”? While expansion is effectively instantaneous, of bilayer-embedded stochastic (thermally activated) so spandex kinetics would be critical. Here we model generic two-state (contracted/expanded) spandexes inspired by known bacterial osmovalves (MscL, MscS) then suggest experimental approaches to test for spandex-like behaviors in these proteins. Modeling shows: 1), depend on the transition state location along an area reaction coordinate; 2), increasing concentration a right-shifts its midpoint (= tension-Boltzmann); 3), with midpoints below activating osmovalve could optimize deployment (required: large midpoint, barrier near expanded state); 4), damp excursions at target tension, and speed, halfway between contracted states; larger Δ-area, more precise maintenance tension; higher concentrations amplitude strain fluctuations). One species not excel both first line of defense partners damper. Possible interactions among closed-open discussed MscS- MscL-like