9o83

Cryo-EM structure of apo rabbit TRPM3 having 1 resting and 3 activated subunits at 37 degrees Celsius

spinqualitylabelsall models 9o83, resolution 3.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9o83 is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.96Å Ligands: Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Detecting noxious heat is vital for survival, triggering protective pain responses. The TRPM3 channel is a key nociceptor and a promising therapeutic target for pain and neurological disorders. Here we show that the rabbit TRPM3 is intrinsically dynamic, with its intracellular domain (ICD) sampling both resting and activated states, but favoring the resting state in the absence of stimulation. We reveal that heat and the synthetic agonist CIM0216 shift the equilibrium toward activation by inducing a similar ICD rearrangement. Mutations that facilitate ICD movement enhance sensitivity to both thermal and chemical stimuli, underscoring the central role of the ICD in channel gating. We also show that the antagonist primidone binds the same site as CIM0216 in the S1-S4 domain but inhibits channel activation. This study provides a structural framework for a mechanistic understanding of thermal and chemical gating of TRPM3 and for guiding the rational design of TRPM3-targeted analgesics and neurotherapeutics. Structural basis for agonist and heat activation of nociceptor TRPM3.,Kumar S, Jin F, Park SJ, Choi W, Keuning SI, Massimino RP, Vu S, Lu W, Du J Nat Struct Mol Biol. 2025 Oct 24. doi: 10.1038/s41594-025-01692-5. PMID:41136608 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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