Titre
Molecular analysis of potential hinge residues in the inactivation gate of brain type IIA Na+ channels.
Type
article
Institution
Externe
Périodique
Auteur(s)
Kellenberger, S.
Auteure/Auteur
West, J.W.
Auteure/Auteur
Catterall, W.A.
Auteure/Auteur
Scheuer, T.
Auteure/Auteur
Liens vers les personnes
ISSN
0022-1295
Statut éditorial
Publié
Date de publication
1997
Volume
109
Numéro
5
Première page
607
Dernière page/numéro d’article
617
Langue
anglais
Résumé
During inactivation of Na+ channels, the intracellular loop connecting domains III and IV is thought to fold into the channel protein and occlude the pore through interaction of the hydrophobic motif isoleucine-phenylalanine-methionine (IFM) with a receptor site. We have searched for amino acid residues flanking the IFM motif which may contribute to formation of molecular hinges that allow this motion of the inactivation gate. Site-directed mutagenesis of proline and glycine residues, which often are components of molecular hinges in proteins, revealed that G1484, G1485, P1512, P1514, and P1516 are required for normal fast inactivation. Mutations of these residues slow the time course of macroscopic inactivation. Single channel analysis of mutations G1484A, G1485A, and P1512A showed that the slowing of macroscopic inactivation is produced by increases in open duration and latency to first opening. These mutant channels also show a higher probability of entering a slow gating mode in which their inactivation is further impaired. The effects on gating transitions in the pathway to open Na+ channels indicate conformational coupling of activation to transitions in the inactivation gate. The results are consistent with the hypothesis that these glycine and proline residues contribute to hinge regions which allow movement of the inactivation gate during the inactivation process of Na+ channels.
Sujets
PID Serval
serval:BIB_C54F25AE1360
PMID
Open Access
Oui
Date de création
2008-01-24T11:45:12.124Z
Date de création dans IRIS
2025-05-20T23:47:08Z