Open AccessDimer interaction in the Hv1 proton channel
Author(s) -
Laetitia Mony,
David Stroebel,
Ehud Y. Isacoff
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2010032117
Subject(s) - dimer , gating , chemistry , biophysics , cooperativity , transmembrane protein , coiled coil , ion channel , transmembrane domain , protein subunit , acid sensing ion channel , mutagenesis , voltage gated ion channel , crystallography , mutation , biochemistry , membrane , biology , receptor , organic chemistry , gene
Significance The Hv1 proton channel is an unusual voltage-gated ion channel with atypical architecture and stoichiometry. While functional as a monomer, Hv1 is usually expressed as a dimer of two voltage-sensing domains (VSDs). How the two VSDs arrange relative to each other is a matter of debate and the functional impact of VSD–VSD interactions is only partly understood. We show that the Hv1 dimer interface is formed by the S1 and S4 transmembrane segments of the VSD. We find this S1–S4 dimer interface to be a strong regulator of Hv1 gating. This interface therefore constitutes a promising target for the development of allosteric modulators for this class of channels critical for pH regulation and immunity.