| Property | Value |
|---|
|
?:abstract
|
-
The human transient receptor potential vanilloid 4 (hTRPV4) ion channel plays a critical role in a variety of biological processes. Whilst the activation of hTRPV4 gating properties has been reported for a broad spectrum of stimuli, including synthetic 4α-phorbols, the molecular basis of the activation is poorly understood. Here we report the novel cryo-EM structure of the hTRPV4 determined in the presence of the archetypical phorbol acid agonist, 4α-PDD. Complementary mutagenesis experiments support the EM-identified binding site as well as allowing rationalization of disruptive mutants located outside of the 4α-PDD binding site. This work represents the first structural information of hTRPV4 in a ligand-induced open conformation. Together, our data reveal the underlying molecular mechanisms resulting in the opening of the central pore and ion-channel activation and provide a structural template for designing inhibitors targeting the open-state conformation of hTRPV4.
|
|
is
?:annotates
of
|
|
|
?:creator
|
|
|
?:doi
|
|
|
?:doi
|
-
10.1101/2020.10.13.334797
|
|
?:externalLink
|
|
|
?:journal
|
|
|
?:license
|
|
|
?:pdf_json_files
|
-
document_parses/pdf_json/419d00e656bde951587b73d8111452e61869ccfb.json
|
|
?:publication_isRelatedTo_Disease
|
|
|
is
?:relation_isRelatedTo_publication
of
|
|
|
?:sha_id
|
|
|
?:source
|
|
|
?:title
|
-
Cryo-EM structural studies of the agonist complexed human TRPV4 ion-channel reveals novel structural rearrangements resulting in an open-conformation
|
|
?:type
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}