9P0N
MscS in Glyco-DIBMA Native Nanodiscs (C7 symmetry)
Summary for 9P0N
| Entry DOI | 10.2210/pdb9p0n/pdb |
| EMDB information | 71088 71089 |
| Descriptor | Small-conductance mechanosensitive channel, (2R)-1-(hexadecanoyloxy)-3-(phosphonooxy)propan-2-yl (9Z)-octadec-9-enoate (3 entities in total) |
| Functional Keywords | mechanosensitive channel, membrane protein, native nanodisc, polymer, glyco-dibma, cryo-em, lipid |
| Biological source | Escherichia coli |
| Total number of polymer chains | 7 |
| Total formula weight | 241160.39 |
| Authors | Moller, E.,Britt, M.,Zhou, F.,Yang, H.,Anishkin, A.,Ernst, R.,Juan, V.M.,Sukharev, S.,Matthies, D. (deposition date: 2025-06-07, release date: 2026-01-28) |
| Primary citation | Moller, E.,Britt, M.,Zhou, F.,Yang, H.,Anishkin, A.,Ernst, R.,Vanegas, J.M.,Sukharev, S.,Matthies, D. The lipid-mediated mechanism of mechanosensitive channel MscS inactivation. Biorxiv, 2025 Cited by PubMed Abstract: Interpretations of experimental conformations of mechanosensitive channels gated by 'force from lipids' become more reliable when native lipids are preserved in the structures. MscS is an adaptive osmolyte release valve that regulates turgor in osmotically stressed cells. MscS promptly opens under abrupt super-threshold tensions in the membrane, but at lower and more gradually applied tensions, it silently inactivates from the closed state. A central question has been whether to assign the commonly observed non-conductive conformation with splayed peripheral helices to a closed or inactivated state. We present a 3-Å MscS cryo-EM structure obtained in Glyco-DIBMA polymers, which avoid complete lipid removal. Within the complex, we observe densities for endogenous phospholipids intercalating between the peripheral and pore-lining helices. The lipidomic analysis shows a 2-3 fold enrichment of phosphatidylglycerol in Glyco-DIBMA-extracted MscS samples. The computed pressure of these lipids on the protein surface enforces the characteristic kinks in the pore-lining helices, sterically stabilizing the separation of the peripheral helices. Mutations of residues coordinating lipids in the crevices eliminate inactivation, allowing us to classify this group of structures as the inactivated state. Our study reveals a novel inactivation mechanism in which intercalated lipids physically decouple the tension-sensing helices from the gate. PubMed: 38328078DOI: 10.1101/2024.01.22.576751 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.99 Å) |
Structure validation
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