8e4q | pdb_00008e4q

The closed C0-state flycatcher TRPM8 structure in complex with PI(4,5)P2

spinqualitylabelsall models 8e4q, resolution 3.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8e4q is a 4 chain structure with sequence from Ficedula albicollis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PIO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function U3JD03_FICAL Publication Abstract from PubMed The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP2-dependent TRPM8 activation. We present cryo-electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP2-dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6-elucidating the molecular basis of chemically induced cool sensation in mammals. Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP2.,Yin Y, Zhang F, Feng S, Butay KJ, Borgnia MJ, Im W, Lee SY Science. 2022 Oct 14;378(6616):eadd1268. doi: 10.1126/science.add1268. Epub 2022 , Oct 14. PMID:36227998 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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