6C8F

Crystal structure of Transient Receptor Potential (TRP) channel TRPV4 in the presence of cesium

Summary for 6C8F

• Entry DOI: 10.2210/pdb6c8f/pdb
• Descriptor: Transient receptor potential cation channel, subfamily V, member 4, CESIUM ION (2 entities in total)
• Functional Keywords: ion channal, transport protein
• Biological source: Xenopus tropicalis (Western clawed frog)
• Total number of polymer chains: 1
• Total formula weight: 77201.58

Authors

Deng, Z.,Paknejad, N.,Maksaev, G.,Sala-Rabanal, M.,Nichols, C.G.,Hite, R.K.,Yuan, P. (deposition date: 2018-01-24, release date: 2018-02-28, Last modification date: 2023-10-04)

Primary citation

Deng, Z.,Paknejad, N.,Maksaev, G.,Sala-Rabanal, M.,Nichols, C.G.,Hite, R.K.,Yuan, P.
Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms.
Nat. Struct. Mol. Biol., 25:252-260, 2018

PubMed Abstract: 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.

PubMed: 29483651
DOI: 10.1038/s41594-018-0037-5

Experimental method

X-RAY DIFFRACTION (6.5 Å)