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TitleSymmetry transitions during gating of the TRPV2 ion channel in lipid membranes.
Journal, issue, pagesElife, Vol. 8, Year 2019
Publish dateMay 15, 2019
AuthorsLejla Zubcevic / Allen L Hsu / Mario J Borgnia / Seok-Yong Lee /
PubMed AbstractThe Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography ...The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here, we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions.
External linksElife / PubMed:31090543 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 4.2 Å
Structure data

20143

6oo3

EMDB-20143, PDB-6oo3:
Cryo-EM structure of the C4-symmetric TRPV2/RTx complex in amphipol resolved to 2.9 A
Method: EM (single particle) / Resolution: 2.9 Å

20145

6oo4

EMDB-20145, PDB-6oo4:
Cryo-EM structure of the C2-symmetric TRPV2/RTx complex in amphipol resolved to 3.3 A
Method: EM (single particle) / Resolution: 3.3 Å

20146

6oo5

EMDB-20146, PDB-6oo5:
Cryo-EM structure of the C2-symmetric TRPV2/RTx complex in amphipol resolved to 4.2 A
Method: EM (single particle) / Resolution: 4.2 Å

20148

6oo7

EMDB-20148, PDB-6oo7:
Cryo-EM structure of the C2-symmetric TRPV2/RTx complex in nanodiscs
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-6EU:
resiniferatoxin / toxin*YM

Source
  • oryctolagus cuniculus (rabbit)
KeywordsMETAL TRANSPORT / ion channel / calcium channel / TRP channel

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