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TitleCryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms.
Journal, issue, pagesNat Struct Mol Biol, Vol. 25, Issue 3, Page 252-260, Year 2018
Publish dateFeb 26, 2018
AuthorsZengqin Deng / Navid Paknejad / Grigory Maksaev / Monica Sala-Rabanal / Colin G Nichols / Richard K Hite / Peng Yuan /
PubMed AbstractThe transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present ...The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity. Structural comparisons with other TRP channels and distantly related voltage-gated cation channels reveal an unprecedented, unique packing interface between the voltage-sensor-like domain and the pore domain, suggesting distinct gating mechanisms. Moreover, our structure begins to provide mechanistic insights to the large set of pathogenic mutations, offering potential opportunities for drug development.
External linksNat Struct Mol Biol / PubMed:29483651 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.8 - 6.5 Å
Structure data

7075

6bbj

EMDB-7075, PDB-6bbj:
Xenopus Tropicalis TRPV4
Method: EM (single particle) / Resolution: 3.8 Å

PDB-6c8f:
Crystal structure of Transient Receptor Potential (TRP) channel TRPV4 in the presence of cesium
Method: X-RAY DIFFRACTION / Resolution: 6.5 Å

PDB-6c8g:
Crystal structure of Transient Receptor Potential (TRP) channel TRPV4 in the presence of barium
Method: X-RAY DIFFRACTION / Resolution: 6.31 Å

PDB-6c8h:
Crystal structure of Transient Receptor Potential (TRP) channel TRPV4 in the presence of gadolinium
Method: X-RAY DIFFRACTION / Resolution: 6.5 Å

Chemicals

ChemComp-CS:
Unknown entry

ChemComp-BA:
Unknown entry

ChemComp-GD:
GADOLINIUM ATOM

Source
  • xenopus tropicalis (tropical clawed frog)
KeywordsMETAL TRANSPORT / Ion Channel / TRP channel / TRANSPORT PROTEIN / ion channal

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