8T3M
TRPV1 in nanodisc bound with 3 LPA molecules
Summary for 8T3M
| Entry DOI | 10.2210/pdb8t3m/pdb |
| EMDB information | 41006 |
| Descriptor | Transient receptor potential cation channel subfamily V member 1, [(2~{R})-2-hexadecanoyloxy-3-[oxidanyl-[(2~{S},3~{S},5~{R},6~{S})-2,3,4,5,6-pentakis(oxidanyl)cyclohexyl]oxy-phosphoryl]oxy-propyl] hexadecanoate, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | trpv1, lysophosphatidic acid, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 4 |
| Total formula weight | 294069.71 |
| Authors | Arnold, W.R.,Julius, D.,Cheng, Y. (deposition date: 2023-06-07, 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 Cited by 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: 38698206DOI: 10.1038/s41594-024-01299-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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