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TitleEukaryotic Kv channel Shaker inactivates through selectivity filter dilation rather than collapse.
Journal, issue, pagesSci Adv, Vol. 9, Issue 49, Page eadj5539, Year 2023
Publish dateDec 8, 2023
AuthorsRobyn Stix / Xiao-Feng Tan / Chanhyung Bae / Ana I Fernández-Mariño / Kenton J Swartz / José D Faraldo-Gómez /
PubMed AbstractEukaryotic voltage-gated K channels have been extensively studied, but the structural bases for some of their most salient functional features remain to be established. C-type inactivation, for ...Eukaryotic voltage-gated K channels have been extensively studied, but the structural bases for some of their most salient functional features remain to be established. C-type inactivation, for example, is an auto-inhibitory mechanism that confers temporal resolution to their signal-firing activity. In a recent breakthrough, studies of a mutant of Shaker that is prone to inactivate indicated that this process entails a dilation of the selectivity filter, the narrowest part of the ion conduction pathway. Here, we report an atomic-resolution cryo-electron microscopy structure that demonstrates that the wild-type channel can also adopt this dilated state. All-atom simulations corroborate this conformation is congruent with the electrophysiological characteristics of the C-type inactivated state, namely, residual K conductance and altered ion specificity, and help rationalize why inactivation is accelerated or impeded by certain mutations. In summary, this study establishes the molecular basis for an important self-regulatory mechanism in eukaryotic K channels, laying a solid foundation for further studies.
External linksSci Adv / PubMed:38064553 / PubMed Central
MethodsEM (single particle)
Resolution2.39 Å
Structure data

41193

8teo

EMDB-41193, PDB-8teo:
Shaker in low K+ (4mM K+)
Method: EM (single particle) / Resolution: 2.39 Å

Chemicals

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM / POPC

ChemComp-K:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • drosophila melanogaster (fruit fly)
KeywordsMEMBRANE PROTEIN / voltage-gated potassium channel

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