⭐ High Impact

Structural insights into the gating mechanisms of TRPV channels.

Pumroy Ruth A, Fluck Edwin C, Ahmed Tofayel, Moiseenkova-Bell Vera Y

📰 Cell calcium 📅 2020 📊 75 citations
DOI PubMed

Abstract

Transient Receptor Potential channels from the vanilloid subfamily (TRPV) are a group of cation channels modulated by a variety of endogenous stimuli as well as a range of natural and synthetic compounds. Their roles in human health make them of keen interest, particularly from a pharmacological perspective. However, despite this interest, the complexity of these channels has made it difficult to obtain high resolution structures until recently. With the cryo-EM resolution revolution, TRPV channel structural biology has blossomed to produce dozens of structures, covering every TRPV family member and a variety of approaches to examining channel modulation. Here, we review all currently available TRPV structures and the mechanistic insights into gating that they reveal.

🔬 Techniques

Cryo-Electron Microscopy

🧬 Organisms

Xenopus laevis Xenopus tropicalis

✨ Fluorophores

DiD

🧪 Sample Preparation

Fixation

🔬 Cell Lines

Primary Epithelial Cells

💾 Data Repositories

PDB 3J5P PDB 3J5R PDB 3J5Q PDB 2PNN PDB 5IRZ PDB 5IRX PDB 5IS0 PDB 5AN8 PDB 5HI9 PDB 6BWJ PDB 6OO3 PDB 6BO4 PDB 6BO5 PDB 6U84 PDB 6U86 PDB 6U8A PDB 6U88 PDB 6DVW PDB 6DVY PDB 6DVZ PDB 6MHO PDB 6MHS PDB 6MHV PDB 6MHW PDB 6OT2 PDB 6OT5 PDB 6PVL PDB 6PVM PDB 6PVN PDB 6PVO PDB 6PVP PDB 6PVQ PDB 6B5V PDB 6DMR PDB 6DMW PDB 6O1P PDB 6O1N PDB 6O1U PDB 6DMU PDB 6O20 PDB 6PBE PDB 6PBF PDB 5IWK PDB 5WO7 PDB 6BO9 PDB 6BO8 PDB 6BOB PDB 6BOA PDB 6D7O PDB 6D7V PDB 6D7T PDB 6D7S PDB 6E2F PDB 6E2G PDB 6C8F PDB 6C8G PDB 6C8H PDB 5WO9 PDB 5WOA PDB 6BBJ PDB 3SUI

🏛️ Research Organizations (ROR)

Affiliated research institutions:

🏛 University of Pennsylvania 🏛 Translational Therapeutics (United States)

📊 Figures

Figure 1.

Figure 1.

Domain architecture and 3-dimensional organization of TRPV channels. (a) Cartoon representation of a TRPV monomer. The N-terminal domain (NTD) is depicted in grey, the ankyrin repeat domain (ARD) in y...

Figure 2.

Figure 2.

Pore diagrams of TRPV1-4. (a) rTRPV1 mi closed (PDB 5IRZ). (b) rTRPV1 mi open (PDB 5IRX). (c) rbTRPV2 mi closed (PDB 5AN8). (d) rTRPV2 semi-open (PDB 6U86). (e) mTRPV3 closed (PDB 6DVW). (f) mTRPV3 Y5...

Figure 3.

Figure 3.

Pore diagrams of TRPV5-6. (a) rbTRPV5 closed (PDB 6DMR). (b) rbTRPV5 open (PDB 6DMU). (c) rTRPV6* closed (PDB 5WO7). (d) rTRPV6 open (PDB 6BOB). Residues of interest depicted as sticks.

Figure 4.

Figure 4.

TRPV mechanisms revealed by structural biology. (a) All open TRPV structures determined so far have a u03c0-helix (purple) in S6 (green). Some of these channels already have a u03c0-helix in their apo...

Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.

🏛️ Imaging Facility

🏛️ University of Pennsylvania

💬 Discussion

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