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- W2028856813 abstract "Macromolecular excluded volume (crowding) is a critical parameter regulated by all cells, but how it is sensed remains unclear. Bacteria avoid dehydration in hypertonic media by accumulating ions and compatible osmolytes, which retain the necessary fraction of free water. Upon dilution of the medium, excess osmolytes are released through tension-activated channels acting as valves. We found that the mechanosensitive channel MscS, which exhibits slow inactivation under moderate tension, inactivates abruptly under the same tension in the presence of cytoplasmic crowders. To study the synergism between tension and crowding, we analyze the features that differentiate the inactivated (crystal-like) conformation from the modeled compact resting state, which include the splayed lipid-facing TM1-TM2 helices uncoupled from the gate and sharp kinks of the pore-lining TM3s at G113 stabilized by association of TM3b segments with the cytoplasmic beta domains. To mimic the effect of crowding, we performed MD simulations in which axial pressure is applied to the bottom of the cytoplasmic (cage) domain toward the membrane. We found that both models exhibit similar axial compliance and the cage reduces its volume in the cytoplasm, however in the inactivated state axial compaction produces a stronger expansion of the TM domain in the plane of the membrane. This concerted shape change appears to be the reason for the thermodynamic coupling of the bulk crowding effect with the energetic input from membrane tension, which both drive channel inactivation. We conclude that cage of MscS is the sensor which provides the feedback on increased crowding and disengages the gate to prevent c ‘over-draining’ of the cytoplasm. We discuss the mechanics of a bacterial cell surrounded by an elastic cell wall where this inhibitory feedback on osmolytes release might be necessary." @default.
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- W2028856813 date "2014-01-01" @default.
- W2028856813 modified "2023-09-28" @default.
- W2028856813 title "The Coupling of Tension and Crowding Sensing in the Bacterial Channel MscS" @default.
- W2028856813 doi "https://doi.org/10.1016/j.bpj.2013.11.3114" @default.
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