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TitleStructure of human TRPM8 channel.
Journal, issue, pagesCommun Biol, Vol. 6, Issue 1, Page 1065, Year 2023
Publish dateOct 19, 2023
AuthorsSergii Palchevskyi / Mariusz Czarnocki-Cieciura / Giulio Vistoli / Silvia Gervasoni / Elżbieta Nowak / Andrea R Beccari / Marcin Nowotny / Carmine Talarico /
PubMed AbstractTRPM8 is a non-selective cation channel permeable to both monovalent and divalent cations that is activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. It ...TRPM8 is a non-selective cation channel permeable to both monovalent and divalent cations that is activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. It is a therapeutic target for anticancer drug development, and its modulators can be utilized for several pathological conditions. Here, we present a cryo-electron microscopy structure of a human TRPM8 channel in the closed state that was solved at 2.7 Å resolution. Our structure comprises the most complete model of the N-terminal pre-melastatin homology region. We also visualized several lipids that are bound by the protein and modeled how the human channel interacts with icilin. Analyses of pore helices in available TRPM structures showed that all these structures can be grouped into different closed, desensitized and open state conformations based on the register of the pore helix S6 which positions particular amino acid residues at the channel constriction.
External linksCommun Biol / PubMed:37857704 / PubMed Central
MethodsEM (single particle)
Resolution2.65 - 3.2 Å
Structure data

EMDB-15981, PDB-8bdc:
Human apo TRPM8 in a closed state (composite map)
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-15982: Human apo TRPM8 in a closed state (consensus map)
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-15983: Human apo TRPM8 in a closed state (focused pre-MHR + MHR1/2 map)
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

ChemComp-UND:
UNDECANE

ChemComp-NA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / calcium ion channel / cold temperature sensor

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