Mutations in the palm domain disrupt modulation of acid-sensing ion channel 1a currents by neuropeptides.

Détails

Ressource 1Télécharger: Bargeton_et_al-2019-Scientific_Reports_.pdf (2825.21 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_3C115A0AD37A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutations in the palm domain disrupt modulation of acid-sensing ion channel 1a currents by neuropeptides.
Périodique
Scientific reports
Auteur(s)
Bargeton B., Iwaszkiewicz J., Bonifacio G., Roy S., Zoete V., Kellenberger S.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
22/02/2019
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
2599
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Modulation by neuropeptides enhances several functions of acid-sensing ion channels (ASICs), such as pain sensation and acid-induced neuronal injury. The acid-induced opening of ASICs is transient, because of a rapid desensitization. Neuropeptides containing an Arg-Phe-amide motif affect ASIC desensitization and allow continuous activity of ASICs. In spite of the importance of the sustained ASIC activity during prolonged acidification, the molecular mechanisms of ASIC modulation by neuropeptides is only poorly understood. To identify the FRRFa (Phe-Arg-Arg-Phe-amide) binding site on ASIC1a, we carried out an in silico docking analysis and verified functionally the docking predictions. The docking experiments indicated three possible binding pockets, located (1) in the acidic pocket between the thumb, finger, β-ball and palm domains, (2) in a pocket at the bottom of the thumb domain, and (3) in the central vestibule along with the connected side cavities. Functional measurements of mutant ASIC1a confirmed the importance of residues of the lower palm, which encloses the central vestibule and its side cavities, for the FRRFa effects. The combined docking and functional experiments strongly suggest that FRRFa binds to the central vestibule and its side cavities to change ASIC desensitization.
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/02/2019 12:32
Dernière modification de la notice
21/08/2019 6:08
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