Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms Journal Article
| Authors: | Deng, Z.; Paknejad, N.; Maksaev, G.; Sala-Rabanal, M.; Nichols, C. G.; Hite, R. K.; Yuan, P. |
| Article Title: | Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms |
| 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. © 2018 The Author(s). |
| Keywords: | controlled study; nonhuman; comparative study; binding site; protein structure; x ray crystallography; x ray diffraction; cryoelectron microscopy; channel gating; ion transport; xenopus tropicalis; priority journal; article; cation channel; vanilloid receptor 4 |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 25 |
| Issue: | 3 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-03-01 |
| Start Page: | 252 |
| End Page: | 260 |
| Language: | English |
| DOI: | 10.1038/s41594-018-0037-5 |
| PROVIDER: | scopus |
| PUBMED: | 29483651 |
| PMCID: | PMC6252174 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 April 2018 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work