Interrogation of the intersubunit interface of the open Hv1 proton channel with a probe of allosteric coupling

Liang Hong, Vikrant Singh, Heike Wulff, Francesco Tombola

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The Hv1 voltage-gated proton channel is a dimeric complex consisting of two voltage-sensing domains (VSDs), each containing a gated proton permeation pathway. Dimerization is controlled by a cytoplasmic coiled-coil domain. The transitions from the closed to the open state in the two VSDs are known to occur cooperatively; however, the underlying mechanism is poorly understood. Intersubunit interfaces play a critical role in allosteric processes; but, such interfaces have not been determined in the open Hv1 channel. Here we show that 2-guanidinothiazole derivatives block the two Hv1 VSDs in a cooperative way, and use one of the compounds as a probe of allosteric coupling between open subunits. We find that the extracellular ends of the first transmembrane segments of the VSDs form the intersubunit interface that mediates coupling between binding sites, while the coiled-coil domain does not directly participate in the process. We also find strong evidence that the channels proton selectivity filter controls blocker binding cooperativity.

Original languageEnglish (US)
Article number14077
JournalScientific Reports
Volume5
DOIs
StatePublished - Sep 14 2015

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Protons
Dimerization
Binding Sites

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Interrogation of the intersubunit interface of the open Hv1 proton channel with a probe of allosteric coupling. / Hong, Liang; Singh, Vikrant; Wulff, Heike; Tombola, Francesco.

In: Scientific Reports, Vol. 5, 14077, 14.09.2015.

Research output: Contribution to journalArticle

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