8FHI
Wildtype rabbit TRPV5 in nanodiscs in complex with oleoyl coenzyme A, Open stated
Summary for 8FHI
| Entry DOI | 10.2210/pdb8fhi/pdb |
| EMDB information | 29086 |
| Descriptor | Transient receptor potential cation channel subfamily V member 5, ERGOSTEROL, S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (9Z)-octadec-9-enethioate (non-preferred name), ... (4 entities in total) |
| Functional Keywords | trpv5, trp channel, oleoyl coenzyme a, open state, membrane protein |
| Biological source | Oryctolagus cuniculus (rabbit) |
| Total number of polymer chains | 4 |
| Total formula weight | 345479.75 |
| Authors | |
| Primary citation | Lee, B.H.,De Jesus Perez, J.J.,Moiseenkova-Bell, V.,Rohacs, T. Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A. Nat Commun, 14:5883-5883, 2023 Cited by PubMed Abstract: Long-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ion channel regulation by LC-CoA is not known. Transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6) are epithelial calcium-selective ion channels. Here, we demonstrate that LC-CoA activates TRPV5 and TRPV6 in inside-out patches, and both exogenously supplied and endogenously produced LC-CoA can substitute for the natural ligand phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) in maintaining channel activity in intact cells. Utilizing cryo-electron microscopy, we determined the structure of LC-CoA-bound TRPV5, revealing an open configuration with LC-CoA occupying the same binding site as PI(4,5)P in previous studies. This is consistent with our finding that PI(4,5)P could not further activate the channels in the presence of LC-CoA. Our data provide molecular insights into ion channel regulation by a metabolic signaling molecule. PubMed: 37735536DOI: 10.1038/s41467-023-41577-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.25 Å) |
Structure validation
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