Structure of the Shaker Kv channel and mechanism of slow C-type inactivation.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
18 Mar 2022
18 Mar 2022
Historique:
entrez:
18
3
2022
pubmed:
19
3
2022
medline:
19
3
2022
Statut:
ppublish
Résumé
Voltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing rates and serves as a form of short-term memory and is implicated in various human neurological disorders. Here, we use high-resolution cryo-electron microscopy and computer simulations to determine one of the molecular mechanisms underlying this physiologically crucial process. Structures of the activated Shaker Kv channel and of its W434F mutant in lipid bilayers demonstrate that C-type inactivation entails the dilation of the ion selectivity filter and the repositioning of neighboring residues known to be functionally critical. Microsecond-scale molecular dynamics trajectories confirm that these changes inhibit rapid ion permeation through the channel. This long-sought breakthrough establishes how eukaryotic K
Identifiants
pubmed: 35302848
doi: 10.1126/sciadv.abm7814
pmc: PMC8932672
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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