TRPV1 structures in distinct conformations reveal mechanisms of activation

By E. Cao, Maofu Liao, Yifan Cheng, D. Julius. Nature, 2013

656 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Sensory Systems

View Paper: https://www.semanticscholar.org/paper/e84bab0175fc5f4a328995092b270cd36a1722de

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. José A. Rodríguez
2. Todd O. Yeates
3. Michael J. Thompson

Citations in the corpus

• Advances in methods for atomic resolution macromolecular structure determination (2020, background): “…in the literature, including structures of ribosomes bound to antibiotics 22 and a TRP channel bound to capsaicin and other vanilloid ligands 23 , highlight the ability of cryo-EM to achieve the resolution needed for structural biology applications in areas such as drug discovery 24 (Figure…”