Titre

Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating.

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Vullo, S.
Auteure/Auteur
Bonifacio, G.
Auteure/Auteur
Roy, S.
Auteure/Auteur
Johner, N.
Auteure/Auteur
Bernèche, S.
Auteure/Auteur
Kellenberger, S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1091-6490
Statut éditorial
Publié
Date de publication
2017-04-04
Volume
114
Numéro
14
Première page
3768
Dernière page/numéro d’article
3773
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Acid-sensing ion channels (ASICs) are proton-activated Na <sup>+</sup> channels expressed in the nervous system, where they are involved in learning, fear behaviors, neurodegeneration, and pain sensation. In this work, we study the role in pH sensing of two regions of the ectodomain enriched in acidic residues: the acidic pocket, which faces the outside of the protein and is the binding site of several animal toxins, and the palm, a central channel domain. Using voltage clamp fluorometry, we find that the acidic pocket undergoes conformational changes during both activation and desensitization. Concurrently, we find that, although proton sensing in the acidic pocket is not required for channel function, it does contribute to both activation and desensitization. Furthermore, protonation-mimicking mutations of acidic residues in the palm induce a dramatic acceleration of desensitization followed by the appearance of a sustained current. In summary, this work describes the roles of potential pH sensors in two extracellular domains, and it proposes a model of acidification-induced conformational changes occurring in the acidic pocket of ASIC1a.
Sujets

Acid Sensing Ion Chan...

Acid Sensing Ion Chan...

Acid Sensing Ion Chan...

Binding Sites

Humans

Hydrogen-Ion Concentr...

Models, Molecular

Mutation

Protein Structure, Te...

Sodium/metabolism

Toxins, Biological/me...

acid-sensing ion chan...

conformational change...

kinetic model

pH sensing

voltage clamp fluorom...

PID Serval
serval:BIB_39E189CDEDD9
DOI
PMID
WOS
Permalien
Open Access
Oui
Date de création
2017-03-28T16:01:43.764Z
Date de création dans IRIS
2025-05-20T17:55:30Z
Fichier(s)
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PNAS-2017-Vullo-3768-73_PDF_Publisher.pdf

Version du manuscrit

published

Taille

4.94 MB

Format

Adobe PDF

PID Serval

serval:BIB_39E189CDEDD9.P003

URN

urn:nbn:ch:serval-BIB_39E189CDEDD94

Somme de contrôle

(MD5):0b21b2995ccb1d140ec0524a36fa2319

En cours de chargement...
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20299463_PostPrint.pdf

Version du manuscrit

postprint

Taille

5.75 MB

Format

Adobe PDF

PID Serval

serval:BIB_39E189CDEDD9.S002

Somme de contrôle

(MD5):cea6af129fe3991bd4bd55395eeed7af