Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.

Détails

Ressource 1Télécharger: BIB_A6BFB1AFAE84.P001.pdf (3113.93 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_A6BFB1AFAE84
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.
Périodique
Journal of Biological Chemistry
Auteur(s)
Gwiazda K., Bonifacio G., Vullo S., Kellenberger S.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
290
Numéro
29
Pages
17956-17966
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.
Mots-clé
ASIC, subunit interaction, disulfide bond, protein-protein interaction, gating, electrophysiology, hydrogen bond, voltage-clamp fluorometry
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/06/2015 13:02
Dernière modification de la notice
20/08/2019 15:11
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