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Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K(+) Channels.

Rauh, Oliver ; Urban, Martin ; Henkes, Leonhard M. ; Winterstein, Tobias ; Greiner, Timo ; Etten, James L. van ; Moroni, Anna ; Kast, Stefan M. ; Thiel, Gerhard ; Schroeder, Indra (2017)
Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K(+) Channels.
In: Journal of the American Chemical Society, 139 (22)
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K(+) channels, KcvS and KcvNTS. These small viral encoded K(+) channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K(+) channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels.

Typ des Eintrags: Artikel
Erschienen: 2017
Autor(en): Rauh, Oliver ; Urban, Martin ; Henkes, Leonhard M. ; Winterstein, Tobias ; Greiner, Timo ; Etten, James L. van ; Moroni, Anna ; Kast, Stefan M. ; Thiel, Gerhard ; Schroeder, Indra
Art des Eintrags: Bibliographie
Titel: Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K(+) Channels.
Sprache: Englisch
Publikationsjahr: 7 Juni 2017
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Journal of the American Chemical Society
Jahrgang/Volume einer Zeitschrift: 139
(Heft-)Nummer: 22
Kurzbeschreibung (Abstract):

Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K(+) channels, KcvS and KcvNTS. These small viral encoded K(+) channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K(+) channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels.

ID-Nummer: pmid:28499087
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Plant Membrane Biophyscis (am 20.12.23 umbenannt in Biologie der Algen und Protozoen)
Hinterlegungsdatum: 05 Jul 2017 06:31
Letzte Änderung: 20 Aug 2021 09:43
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