7LPB

Cryo-EM structure of full-length TRPV1 with capsaicin at 25 degrees Celsius

Summary for 7LPB

• Entry DOI: 10.2210/pdb7lpb/pdb
• EMDB information: 23475
• 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: heat sensing ion channel, membrane protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 413793.27

Authors

Kwon, D.H.,Zhang, F.,Suo, Y.,Lee, S.-Y. (deposition date: 2021-02-11, release date: 2021-07-28)

Primary citation

Kwon, D.H.,Zhang, F.,Suo, Y.,Bouvette, J.,Borgnia, M.J.,Lee, S.Y.
Heat-dependent opening of TRPV1 in the presence of capsaicin.
Nat.Struct.Mol.Biol., 28:554-563, 2021

PubMed Abstract: Transient receptor potential vanilloid member 1 (TRPV1) is a Ca-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. Using cryo-EM, we have determined the structures of apo and capsaicin-bound full-length rat TRPV1 reconstituted into lipid nanodiscs over a range of temperatures. This has allowed us to visualize the noxious heat-induced opening of TRPV1 in the presence of capsaicin. Notably, noxious heat-dependent TRPV1 opening comprises stepwise conformational transitions. Global conformational changes across multiple subdomains of TRPV1 are followed by the rearrangement of the outer pore, leading to gate opening. Solvent-accessible surface area analyses and functional studies suggest that a subset of residues form an interaction network that is directly involved in heat sensing. Our study provides a glimpse of the molecular principles underlying noxious physical and chemical stimuli sensing by TRPV1, which can be extended to other thermal sensing ion channels.

PubMed: 34239123
DOI: 10.1038/s41594-021-00616-3

Experimental method

ELECTRON MICROSCOPY (3.54 Å)