9e68 | pdb_00009e68
Cryo-EM structure of MscS/YnaI chimera in DOPC nanodiscs
Structural highlights
FunctionMSCS_ECOLI Mechanosensitive channel that participates in the regulation of osmotic pressure changes within the cell, opening in response to stretch forces in the membrane lipid bilayer, without the need for other proteins. Forms an ion channel of 1.0 nanosiemens conductance with a slight preference for anions. The channel is sensitive to voltage; as the membrane is depolarized, less tension is required to open the channel and vice versa. The channel is characterized by short bursts of activity that last for a few seconds. The channel pore is formed by TM3 and the loop between TM2 and TM3. After a sharp turn at Gly-113, an alpha-helix (residues 114-127) is oriented nearly parallel to the plane of the putative lipid bilayer. On the intracellular side of the channel, the permeation pathway of MscS does not connect directly to the cytoplasm but instead opens to a large chamber that is connected to the cytoplasm. This chamber resembles a molecular filter that could serve to prescreen large molecules before they are allowed passage to the transmembrane pore. The TM1 and TM2 helices appear to be likely candidates for mediating the tension and voltage sensitivities of MscS. Gating requires large rearrangements of at least the C-terminus.YNAI_ECO57 Publication Abstract from PubMedYnaI is a member of the family of bacterial MscS (mechanosensitive channel of small conductance)-like channels. Channel gating upon hypoosmotic stress and the role of lipids in this process have been extensively studied for MscS, but are less well understood for YnaI, which features two additional transmembrane helices. Here, we combined cryogenic electron microscopy, molecular dynamics simulations and patch-clamp electrophysiology to advance our understanding of YnaI. The two additional helices move the lipid-filled hydrophobic pockets in YnaI further away from the lipid bilayer and change the function of the pocket lipids from being a critical gating element in MscS to being more of a structural element in YnaI. Unlike MscS, YnaI shows pronounced gating hysteresis and remains open to a substantially lower membrane tension than is needed to initially open the channel. Thus, at near-lytic membrane tension, both MscL and YnaI will open, but while MscL has a large pore and must close quickly to minimize loss of essential metabolites, YnaI only conducts ions and can thus remain open for longer to continue to facilitate pressure equilibration across the membrane. Lipid interactions and gating hysteresis suggest a physiological role for mechanosensitive channel YnaI.,Will N, Hiotis G, Nakayama Y, Angiulli G, Zhou Z, Cox CD, Martinac B, Walz T Nat Commun. 2025 Aug 12;16(1):7472. doi: 10.1038/s41467-025-62805-8. PMID:40796571[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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