6nr2 | pdb_00006nr2

Cryo-EM structure of the TRPM8 ion channel in complex with the menthol analog WS-12 and PI(4,5)P2

Loading... Status: waiting for Mol* initialization Structural highlights 6nr2 is a 4 chain structure with sequence from Collared flycatcher. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: KXP, KXS NonStd Res: UNK Gene: TRPM8 (Collared flycatcher) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Transient receptor potential melastatin member 8 (TRPM8) is a Ca(2+)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2), but lack of structural information has thus far precluded a mechanistic understanding of ligand and lipid sensing by TRPM8. Using cryo-electron microscopy, we determined the structures of TRPM8 in complex with the synthetic cooling compound icilin, PIP2, and Ca(2+) and in complex with the menthol analog WS-12 and PIP2 Our structures reveal the binding sites for cooling agonists and PIP2 in TRPM8. Notably, PIP2 binds to TRPM8 in two different modes, which illustrate the mechanism of allosteric coupling between PIP2 and agonists. This study provides a platform for understanding the molecular mechanism of TRPM8 activation by cooling agents. Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel.,Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY Science. 2019 Feb 7. pii: science.aav9334. doi: 10.1126/science.aav9334. PMID:30733385 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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