# Activation and desensitization of heat-sensor TRPV1

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $360,256

## Abstract

Project Summary
Heat- and capsaicin-activated ion channel TRPV1 is an important cellular sensor for maintaining
normal body temperature and detecting noxious ambient environment, hence an important drug target.
TRPV1 also serves as a prototypical model for understanding polymodal activation of diverse TRP
channels. Structures of TRPV1 have been solved by cryo-electron microscopy (cyro-EM) at up-to-2.9-
Å resolutions, yet mechanistic understanding of channel activation, in particular by heat, remains
preliminary. A major limitation has been the lack of effective tools for probing structural dynamics in
functional channels. We have recently identified two structurally related peptide toxins from the venom
of Chinese red-headed centipede, termed RhTx1 and RhTx2, that exhibit highly specific and sub-μM
affinity binding to the outer pore region of TRPV1. Interestingly, while RhTx1 strongly activates the
channel, RhTx2, having just four additional amino acids at its N-terminus, is a potent inhibitor. Our
preliminary study further suggested that RhTx1 specifically promotes heat activation. Because these
small, compact peptide toxins can be readily synthesized and modified, they offer unique opportunities
to probe the molecular mechanism underlying TRPV1 activation, with their rapid ON and OFF kinetics
being particularly favorable for biophysical investigation. The proposed study will take advantage of
these novel toxins to gain a better understanding of TRPV1 activation mechanism by revealing its
structural dynamics using a multidisciplinary approach combines structural, electrophysiological,
optical, and computational modeling methods.

## Key facts

- **NIH application ID:** 10471997
- **Project number:** 5R01GM132110-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** VLADIMIR M YAROV-YAROVOY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $360,256
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471997

## Citation

> US National Institutes of Health, RePORTER application 10471997, Activation and desensitization of heat-sensor TRPV1 (5R01GM132110-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10471997. Licensed CC0.

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