dc.contributor.author |
Berna-Erro, Alejandro |
dc.contributor.author |
Izquierdo-Serra, Mercè |
dc.contributor.author |
Sepúlveda, Romina V. |
dc.contributor.author |
Rubio-Moscardo, Fanny |
dc.contributor.author |
Doñate-Macian, Pablo |
dc.contributor.author |
Serra, Selma A. |
dc.contributor.author |
Carrillo-García, Julia |
dc.contributor.author |
Peralvarez-Marin, Alex |
dc.contributor.author |
González-Nilo, Fernando |
dc.contributor.author |
Fernández-Fernández, José M. |
dc.contributor.author |
Valverde, Miguel A. |
dc.date |
2017 |
dc.identifier |
https://ddd.uab.cat/record/253976 |
dc.identifier |
urn:10.1038/s41598-017-11274-1 |
dc.identifier |
urn:oai:ddd.uab.cat:253976 |
dc.identifier |
urn:pmcid:PMC5585255 |
dc.identifier |
urn:pmc-uid:5585255 |
dc.identifier |
urn:pmid:28874838 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:5585255 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/06d9185b-aa7d-4a94-ae2d-341a49392326 |
dc.identifier |
urn:scopus_id:85028861497 |
dc.identifier |
urn:articleid:20452322v7p10522 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Ministerio de Economía y Competitividad SAF2015-69762-R |
dc.relation |
Ministerio de Economía y Competitividad MDM-2014-0370 |
dc.relation |
Scientific reports ; Vol. 7 (Sep. 2017), art. 10522 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.subject |
Ionc hannel signalling |
dc.subject |
Vasodilation |
dc.title |
Structural determinants of 5',6'-epoxyeicosatrienoic acid binding to and activation of TRPV4 channel |
dc.type |
Article |
dc.description.abstract |
TRPV4 cation channel activation by cytochrome P450-mediated derivatives of arachidonic acid (AA), epoxyeicosatrienoic acids (EETs), constitute a major mechanisms of endothelium-derived vasodilatation. Besides, TRPV4 mechano/osmosensitivity depends on phospholipase A (PLA) activation and subsequent production of AA and EETs. However, the lack of evidence for a direct interaction of EETs with TRPV4 together with claims of EET-independent mechanical activation of TRPV4 has cast doubts on the validity of this mechanism. We now report: 1) The identification of an EET-binding pocket that specifically mediates TRPV4 activation by 5',6'-EET, AA and hypotonic cell swelling, thereby suggesting that all these stimuli shared a common structural target within the TRPV4 channel; and 2) A structural insight into the gating of TRPV4 by a natural agonist (5',6'-EET) in which K535 plays a crucial role, as mutant TRPV4-K535A losses binding of and gating by EET, without affecting GSK1016790A, 4α-phorbol 12,13-didecanoate and heat mediated channel activation. Together, our data demonstrates that the mechano- and osmotransducing messenger EET gates TRPV4 by a direct action on a site formed by residues from the S2-S3 linker, S4 and S4-S5 linker. |