8U3J

TRPV1 in nanodisc bound with empty vanilloid binding pocket at 4C

Summary for 8U3J

• Entry DOI: 10.2210/pdb8u3j/pdb
• EMDB information: 41864
• Descriptor: Transient receptor potential cation channel subfamily V member 1, 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE, SODIUM ION, ... (4 entities in total)
• Functional Keywords: trpv1 in nanodisc bound with empty vanilloid binding pocket at 4c, membrane protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 4
• Total formula weight: 249072.67

Authors

Arnold, W.R.,Julius, D.,Cheng, Y. (deposition date: 2023-09-07, release date: 2024-05-08, Last modification date: 2024-10-02)

Primary citation

Arnold, W.R.,Mancino, A.,Moss 3rd, F.R.,Frost, A.,Julius, D.,Cheng, Y.
Structural basis of TRPV1 modulation by endogenous bioactive lipids.
Nat.Struct.Mol.Biol., 31:1377-1385, 2024

PubMed Abstract: TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel. Here we show that this regulatory pocket in rat TRPV1 can accommodate diverse lipid species, including the inflammatory lipid lysophosphatidic acid, whose actions are determined by their specific modes of binding. Furthermore, we show that an empty-pocket channel lacking an endogenous phosphoinositide lipid assumes an agonist-like state, even at low temperature, substantiating the concept that phosphoinositide lipids serve as negative TRPV1 modulators whose ejection from the binding pocket is a critical step toward activation by thermal or chemical stimuli.

PubMed: 38698206
DOI: 10.1038/s41594-024-01299-2

Experimental method

ELECTRON MICROSCOPY (2.9 Å)