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- W2080709174 abstract "MscS is the major osmolyte efflux valve that regulates turgor in many walled organisms from bacteria to higher plants. The crystal structure of WT E. coli MscS revealed a tight packing of seven pore-lining TM3 helices mediated by conserved Ala-Gly motifs. Complementarity of helical interfaces still leaves a 6.5Å unoccluded pore in the hydrophobic constriction (gate) formed by two rings of leucines. Initial computational studies suggested that that the gate is dehydrated and the crystal conformation should be non-conductive. Our further analysis indicated that the ‘outer chamber’ flanking the gate from the periplasmic side may also be dehydrated, producing a ‘vapor plug’ ∼20Å long. Experimental analysis of hydrophilic substitutions in the outer chamber revealed decreases in the tension threshold and in-plane protein expansion on opening suggesting that the outer chamber is likely to be dehydrated at rest. The data reveal the principle difference between physical closure of the gate with the backbone-attached side chains and occlusion by vapor: water is mobile and after the breakage of the continuous phase it can freely search for new energy minima setting new boundaries and stabilizing nonconductive states. Under membrane tension of ∼5-8 mN/m,MscS opens a 16Å pore that is fully hydrated. The opening transition begins with expansion of water-vapor interfaces, proceeding through wetting of the outer chamber and partial separation of TM3s, which ultimately leads to complete wetting of the hydrophobic pore. We discuss specifically the role of conserved glycines in TM3, which are buried in narrow closed conformations but exposed in the open states that critically changes the wetting characteristics of the pore lining from hydrophobic to hydrophilic and stabilize the conductive state of the channel. We discuss a similar open-state stabilizing mechanism in MscL." @default.
- W2080709174 created "2016-06-24" @default.
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- W2080709174 date "2011-02-01" @default.
- W2080709174 modified "2023-09-25" @default.
- W2080709174 title "Hydration Properties of Mechanosensitive Channel Pores: Dewetting and Stabilization of Conductive States" @default.
- W2080709174 doi "https://doi.org/10.1016/j.bpj.2010.12.243" @default.
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