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Papers of the Week

Papers: 16 Sep 2023 - 22 Sep 2023

Basic Science


2023 Sep 19

J Biol Chem


The Capsaicin Binding Affinity of Wild-Type and Mutant TRPV1 Ion Channels.


Li S, Zheng J


Vanilloids such as capsaicin and resiniferatoxin (RTX) are highly selective and potent activators for TRPV1, a nociceptor for heat and pain perception. However, the intrinsic vanilloid binding affinity, key for understanding TRPV1 function, remains unknown despite intensive investigations by electrophysiological, structural, and computational methods. In this study, we determined capsaicin binding affinity under physiological conditions by isolating individual binding steps with concatemers. We estimated the capsaicin association constant of a wildtype subunit to be in the order of 10 M, and that of the Y511A mutant subunit to be a hundred times lower, in the order of 10 M. The Y511A mutation, located at the entrance of the vanilloid binding pocket, reduces binding affinity without a noticeable effect on activation gating. We further affirmed that there is little cooperativity between vanilloid binding steps. Models based on independent binding and equally cooperative subunit gating can accurately describe capsaicin activation.