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001-es BibID:	BIBFORM112395
035-os BibID:	(scopus)85159838046 (cikkazonosító)e202313352
Első szerző:	Szántó Gábor Tibor (vegyész)
Cím:	Molecular rearrangements in S6 during slow inactivation in Shaker-IR potassium channels / Szanto Tibor G., Papp Ferenc, Zakany Florina, Varga Zoltan, Deutsch Carol, Panyi Gyorgy
Dátum:	2023
ISSN:	0022-1295 1540-7748
Megjegyzések:	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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk potassium channels
Megjelenés:	Journal Of General Physiology. - 155 : 7 (2023), p. 1-14. -
További szerzők:	Papp Ferenc (1979-) (biofizikus) Zákány Florina (1989-) (általános orvos) Varga Zoltán (1969-) (biofizikus, szakfordító) Deutsch, Carol Panyi György (1966-) (biofizikus)
Pályázati támogatás:	KTIA_NAP_13-2-2015-0009 MTA KTIA_ NAP_13-2-2017-0013 MTA K132906 OTKA K143071 OTKA EFOP-3.6.2-16-2017-00006 EFOP GINOP-2.3.2-15-2016-00044 GINOP R01 GM052302 Egyéb
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