7S8B
Cryo-EM structure of human TRPV6 in complex with channel blocker ruthenium red
Summary for 7S8B
| Entry DOI | 10.2210/pdb7s8b/pdb |
| Related | 7S88 7S89 |
| EMDB information | 24890 24891 24892 |
| Descriptor | Transient receptor potential cation channel subfamily V member 6, CHOLESTEROL HEMISUCCINATE, 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (6 entities in total) |
| Functional Keywords | transient receptor potential v family member 6, trp, channel, ruthenium red, channel blocker, antagonist, cnw11, nanodiscs, trpv6, membrane protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 344556.24 |
| Authors | Nadezhdin, K.D.,Neuberger, A.,Sobolevsky, A.I. (deposition date: 2021-09-17, release date: 2021-11-17, Last modification date: 2024-06-05) |
| Primary citation | Neuberger, A.,Nadezhdin, K.D.,Sobolevsky, A.I. Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole. Nat Commun, 12:6284-6284, 2021 Cited by PubMed Abstract: TRPV6 is a calcium-selective ion channel implicated in epithelial Ca uptake. TRPV6 inhibitors are needed for the treatment of a broad range of diseases associated with disturbed calcium homeostasis, including cancers. Here we combine cryo-EM, calcium imaging, and mutagenesis to explore molecular bases of human TRPV6 inhibition by the antifungal drug econazole and the universal ion channel blocker ruthenium red (RR). Econazole binds to an allosteric site at the channel's periphery, where it replaces a lipid. In contrast, RR inhibits TRPV6 by binding in the middle of the ion channel's selectivity filter and plugging its pore like a bottle cork. Despite different binding site locations, both inhibitors induce similar conformational changes in the channel resulting in closure of the gate formed by S6 helices bundle crossing. The uncovered molecular mechanisms of TRPV6 inhibition can guide the design of a new generation of clinically useful inhibitors. PubMed: 34725357DOI: 10.1038/s41467-021-26608-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.43 Å) |
Structure validation
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