Noncanonical electromechanical coupling paths in cardiac hERG potassium channel.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 02 2023
27 02 2023
Historique:
received:
11
10
2022
accepted:
15
02
2023
entrez:
27
2
2023
pubmed:
28
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Voltage-gated potassium channels are involved in many physiological processes such as nerve impulse transmission, the heartbeat, and muscle contraction. However, for many of them the molecular determinants of the gating mechanism remain elusive. Here, using a combination of theoretical and experimental approaches, we address this problem focusing on the cardiac hERG potassium channel. Network analysis of molecular dynamics trajectories reveals the presence of a kinematic chain of residues that couples the voltage sensor domain to the pore domain and involves the S4/S1 and S1/S5 subunit interfaces. Mutagenesis experiments confirm the role of these residues and interfaces in the activation and inactivation mechanisms. Our findings demonstrate the presence of an electromechanical transduction path crucial for the non-domain-swapped hERG channel gating that resembles the noncanonical path identified in domain-swapped K
Identifiants
pubmed: 36849440
doi: 10.1038/s41467-023-36730-7
pii: 10.1038/s41467-023-36730-7
pmc: PMC9971164
doi:
Substances chimiques
Potassium Channels, Voltage-Gated
0
KCNH2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1110Informations de copyright
© 2023. The Author(s).
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