Molecular rearrangements in S6 during slow inactivation in Shaker-IR potassium channels.
Journal
The Journal of general physiology
ISSN: 1540-7748
Titre abrégé: J Gen Physiol
Pays: United States
ID NLM: 2985110R
Informations de publication
Date de publication:
03 07 2023
03 07 2023
Historique:
received:
29
01
2023
revised:
14
04
2023
accepted:
04
05
2023
medline:
24
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
Voltage-gated K+ channels have distinct gates that regulate ion flux: the activation gate (A-gate) formed by the bundle crossing of the S6 transmembrane helices and the slow inactivation gate in the selectivity filter. These two gates are bidirectionally coupled. If coupling involves the rearrangement of the S6 transmembrane segment, then we predict state-dependent changes in the accessibility of S6 residues from the water-filled cavity of the channel with gating. To test this, we engineered cysteines, one at a time, at S6 positions A471, L472, and P473 in a T449A Shaker-IR background and determined the accessibility of these cysteines to cysteine-modifying reagents MTSET and MTSEA applied to the cytosolic surface of inside-out patches. We found that neither reagent modified either of the cysteines in the closed or the open state of the channels. On the contrary, A471C and P473C, but not L472C, were modified by MTSEA, but not by MTSET, if applied to inactivated channels with open A-gate (OI state). Our results, combined with earlier studies reporting reduced accessibility of residues I470C and V474C in the inactivated state, strongly suggest that the coupling between the A-gate and the slow inactivation gate is mediated by rearrangements in the S6 segment. The S6 rearrangements are consistent with a rigid rod-like rotation of S6 around its longitudinal axis upon inactivation. S6 rotation and changes in its environment are concomitant events in slow inactivation of Shaker KV channels.
Identifiants
pubmed: 37212728
pii: 214121
doi: 10.1085/jgp.202313352
pmc: PMC10202832
pii:
doi:
Substances chimiques
Shaker Superfamily of Potassium Channels
0
methanethiosulfonate ethylammonium
0
Ethyl Methanesulfonate
9H154DI0UP
Potassium Channels, Voltage-Gated
0
Cysteine
K848JZ4886
Potassium
RWP5GA015D
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM052302
Pays : United States
Informations de copyright
© 2023 Szanto et al.
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