Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
24 02 2022
24 02 2022
Historique:
received:
08
07
2021
accepted:
25
01
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
5
4
2022
Statut:
epublish
Résumé
The elusive activation/deactivation mechanism of hERG is investigated, a voltage-gated potassium channel involved in severe inherited and drug-induced cardiac channelopathies, including the Long QT Syndrome. Firstly, the available structural data are integrated by providing a homology model for the closed state of the channel. Secondly, molecular dynamics combined with a network analysis revealed two distinct pathways coupling the voltage sensor domain with the pore domain. Interestingly, some LQTS-related mutations known to impair the activation/deactivation mechanism are distributed along the identified pathways, which thus suggests a microscopic interpretation of their role. Split channels simulations clarify a surprising feature of this channel, which is still able to gate when a cut is introduced between the voltage sensor domain and the neighboring helix S5. In summary, the presented results suggest possible activation/deactivation mechanisms of non-domain-swapped potassium channels that may aid in biomedical applications.
Identifiants
pubmed: 35210539
doi: 10.1038/s42003-022-03074-9
pii: 10.1038/s42003-022-03074-9
pmc: PMC8873449
doi:
Substances chimiques
ERG1 Potassium Channel
0
Ether-A-Go-Go Potassium Channels
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
165Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 803213
Informations de copyright
© 2022. The Author(s).
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