7RQV

Cryo-EM structure of the full-length TRPV1 with RTx at 4 degrees Celsius, in an intermediate-closed state, class II

Summary for 7RQV

• Entry DOI: 10.2210/pdb7rqv/pdb
• EMDB information: 24637
• Descriptor: Transient receptor potential cation channel subfamily V member 1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate, ... (5 entities in total)
• Functional Keywords: ligand-gating ion channel, membrane protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 409096.10

Authors

Kwon, D.H.,Suo, Y.,Lee, S.-Y. (deposition date: 2021-08-08, release date: 2022-06-01)

Primary citation

Kwon, D.H.,Zhang, F.,Fedor, J.G.,Suo, Y.,Lee, S.Y.
Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.
Nat Commun, 13:2874-2874, 2022

PubMed Abstract: Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods and cryo-EM in an attempt to obtain temporal resolution of the conformational trajectory of the vanilloid receptor TRPV1 with resiniferatoxin (RTx) bound. Based on our cryo-EM ensemble analysis, RTx binding to TRPV1 appears to induce intracellular gate opening first, followed by selectivity filter dilation, then pore loop rearrangement to reach the final open state. This apparent conformational wave likely arises from the concerted, stepwise, additive structural changes of TRPV1 over many subdomains. Greater understanding of the RTx-mediated long-range allostery of TRPV1 could help further the therapeutic potential of RTx, which is a promising drug candidate for pain relief associated with advanced cancer or knee arthritis.

PubMed: 35610228
DOI: 10.1038/s41467-022-30602-2

Experimental method

ELECTRON MICROSCOPY (3.45 Å)