3J5R

Reconstruction of TRPV1 ion channel in complex with capsaicin by single particle cryo-microscopy

Summary for 3J5R

• Entry DOI: 10.2210/pdb3j5r/pdb
• Related: 3J5P 3J5Q
• EMDB information: 5776 5777 5778
• Descriptor: Transient receptor potential cation channel subfamily V member 1 (1 entity in total)
• Functional Keywords: trpv1 channel, capsaicin, transport protein
• Biological source: Rattus norvegicus (rat)
• Total number of polymer chains: 4
• Total formula weight: 272968.62

Authors

Liao, M.,Cao, E.,Julius, D.,Cheng, Y. (deposition date: 2013-10-28, release date: 2013-12-04, Last modification date: 2024-02-21)

Primary citation

Cao, E.,Liao, M.,Cheng, Y.,Julius, D.
TRPV1 structures in distinct conformations reveal activation mechanisms.
Nature, 504:113-118, 2013

PubMed Abstract: Transient receptor potential (TRP) channels are polymodal signal detectors that respond to a wide range of physical and chemical stimuli. Elucidating how these channels integrate and convert physiological signals into channel opening is essential to understanding how they regulate cell excitability under normal and pathophysiological conditions. Here we exploit pharmacological probes (a peptide toxin and small vanilloid agonists) to determine structures of two activated states of the capsaicin receptor, TRPV1. A domain (consisting of transmembrane segments 1-4) that moves during activation of voltage-gated channels remains stationary in TRPV1, highlighting differences in gating mechanisms for these structurally related channel superfamilies. TRPV1 opening is associated with major structural rearrangements in the outer pore, including the pore helix and selectivity filter, as well as pronounced dilation of a hydrophobic constriction at the lower gate, suggesting a dual gating mechanism. Allosteric coupling between upper and lower gates may account for rich physiological modulation exhibited by TRPV1 and other TRP channels.

PubMed: 24305161
DOI: 10.1038/nature12823

Experimental method

ELECTRON MICROSCOPY (4.2 Å)