Structure of TRPV1 Revealed by Cryo-Electron Microscopy

High-Resolution Structure of TRPV1 Revealed by Cryo-Electron Microscopy | Pain Research Forum

A heat-activated channel and the receptor for capsaicin (the pungent heat in chili peppers), TRPV1 (then called VR1), was already appreciated as a key molecule in pain and a viable target for analgesic therapies, and its genetic identification gave researchers the ability to study the enigmatic channel’s relation to pain sensation.

TRPV1 is not only the key sensor of acute heat pain, but also—and perhaps more importantly in terms of pain treatment—serves as a signal integrator that contributes to chronic pain sensitivity. The newly solved structure will give researchers tools to probe the complexities of TRPV1 regulation and design better TRPV1-targeted therapies. 

The work marks the first time that cryo-EM has achieved such a high-resolution look at a small, transmembrane protein

Although TRP channels bear little functional or sequence resemblance to their voltage-gated kin, scientists had predicted that the overall structure of TRPV1 would resemble potassium and sodium channels, which have been solved by X-ray crystallograph

As pain therapies, TRPV1 blockers carry the danger that they interfere with normal, protective heat sensation

Past studies have suggested that the outer pore domain might be the best locus to target pain sensitization without affecting the heat sensor. “Those are the drugs you want,” Julius said, “and perhaps the new structure will allow researchers to dock compounds in the channel and see where to best target hypersensitivity.



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