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TitleThe bacterial mechanosensitive channel MscM gates through concerted changes in its transmembrane and cytoplasmic domains.
Journal, issue, pagesNat Commun, Year 2026
Publish dateJul 22, 2026
AuthorsGiorgos Hiotis / Thomas Walz /
PubMed AbstractThe mechanosensitive channel of small conductance (MscS) is the founding member of the family of MscS-like channels, which share a structurally conserved core but feature additional structural ...The mechanosensitive channel of small conductance (MscS) is the founding member of the family of MscS-like channels, which share a structurally conserved core but feature additional structural elements that define their specific channel characteristics. Here, we characterize the structure and function of the Escherichia coli mechanosensitive channel of mini conductance (MscM), which features eight additional transmembrane (TM) helices and a large periplasmic domain. Our cryo-EM structures reveal that channel gating involves conformational changes in all domains of MscM. In particular, a cytoplasmic extension of TM7 couples the conformation of the TM domain to that of the cytoplasmic domain, resulting in gating of its lateral fenestrations, where ions enter the channel. Thus, different from all other MscS-like channels studied to date, channel gating in MscM is mediated by its cytoplasmic domain and not the TM domain, which senses changes in membrane tension and operates the cytoplasmic gates.
External linksNat Commun / PubMed:42481478
MethodsEM (single particle)
Resolution2.8 - 6.7 Å
Structure data

EMDB-76005: EcMscM in NaCl in a closed conformation
Method: EM (single particle) / Resolution: 6.7 Å

EMDB-76007, PDB-11sm:
Core of EcMscM in NaCl in a closed conformation
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-76009, PDB-11so:
EcMscM lacking the first periplasmic helical bundle in NaCl in a closed conformation
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-76010: Core of EcMscM lacking the first periplasmic helical bundle in NaCl in a closed conformation
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-76011: EcMscM in KCl in an open conformation
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-76013: EcMscM in KCl in an open conformation, C1 processed
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-76015: EcMscM in KCl in an open conformation with density for the second periplasmic helical bundle
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-76016, PDB-11sq:
EcMscM in KCl in an open conformation, composite structure
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-76017: EcMscM lacking the first periplasmic helical bundle in KCl in an open conformation
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-76018, PDB-11sr:
EcMscM lacking the first periplasmic helical bundle and the cytoplasmic extension of TM7 in NaCl in a closed conformation
Method: EM (single particle) / Resolution: 5.1 Å

EMDB-76019: Core of EcMscM lacking the first periplasmic helical bundle and the cytoplasmic extension of TM7 in NaCl in a closed conformation
Method: EM (single particle) / Resolution: 3.5 Å

Source
  • escherichia coli k-12 (bacteria)
KeywordsMEMBRANE PROTEIN / Mechanosensitive / Ion channel / MscS

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