Abstract

Transient receptor potential vanilloid (TRPV) channels are part of the superfamily of TRP ion channels and play important roles in widespread physiological processes including both neuronal and non‐neuronal pathways. Various diseases such as skeletal abnormalities, chronic pain, and cancer are associated with dysfunction of a TRPV channel. In order to obtain full understanding of disease pathogenesis and create opportunities for therapeutic intervention, it is essential to unravel how these channels function at a molecular level. In the past decade, incredible progress has been made in biochemical sample preparation of large membrane proteins and structural biology techniques, including cryo‐electron microscopy. This has resulted in high resolution structures of all TRPV channels, which has provided novel insights into the molecular mechanisms of channel gating and regulation that will be summarized in this review.

Highlights

  • Mark K. van Goor and Leanne de Jager contributed to this study

  • It has provided us with the first steps towards the dynamics behind channel gating and how ligands and lipids play a role in this process

  • It has already been shown that thorough analysis of cryogenic-electron microscopy (cryo-EM) data can provide valuable insights into channel gating and accompanying structural states, as demonstrated in recent studies by Zubcevic et al.[27,60]

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Summary

Introduction

Mark K. van Goor and Leanne de Jager contributed to this study. Yifan Cheng is the winner of the 2018 Christian B. Channel subfamilies in mammals, the canonical (TRPC), melastatin (TRPM), vanilloid (TRPV), polycystin (TRPP), ankyrin (TRPA), and mucolipin (TRPML) channels, for a total of 28 mammalian family members.[1] Most TRP channels are relatively nonselective cation (mainly calcium) channels. They are distantly related to voltage-gated ion channels (VGICs), a group of ion channels that share a voltage-dependent activation mechanism. Single TRP channel members are often able to sense multiple environmental factors and are considered polymodal sensors of the environment. The development of efficient drugs targeting TRP channels has been slow, partly due to the fact that there were no high-resolution TRP channel structures available

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