Functionality of the Voltage-gated Proton Channel Truncated in S4

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Dec 19

PMID 20018719

Citations 33

Authors

Souhei Sakata

Tatsuki Kurokawa

Morten H H Norholm

Masahiro Takagi

Yoshifumi Okochi

Gunnar von Heijne

Yasushi Okamura

Affiliations

Soon will be listed here.

Abstract

The voltage sensor domain (VSD) is the key module for voltage sensing in voltage-gated ion channels and voltage-sensing phosphatases. Structurally, both the VSD and the recently discovered voltage-gated proton channels (Hv channels) voltage sensor only protein (VSOP) and Hv1 contain four transmembrane segments. The fourth transmembrane segment (S4) of Hv channels contains three periodically aligned arginines (R1, R2, R3). It remains unknown where protons permeate or how voltage sensing is coupled to ion permeation in Hv channels. Here we report that Hv channels truncated just downstream of R2 in the S4 segment retain most channel properties. Two assays, site-directed cysteine-scanning using accessibility of maleimide-reagent as detected by Western blotting and insertion into dog pancreas microsomes, both showed that S4 inserts into the membrane, even if it is truncated between the R2 and R3 positions. These findings provide important clues to the molecular mechanism underlying voltage sensing and proton permeation in Hv channels.

Citing Articles

Trapping Charge Mechanism in Hv1 Channels (Hv1).

Fernandez M, Alvear-Arias J, Carmona E, Carrillo C, Pena-Pichicoi A, Hernandez-Ochoa E Int J Mol Sci. 2024; 25(1).

PMID: 38203601 PMC: 10779229. DOI: 10.3390/ijms25010426.

Voltage-Gated Proton Channels in the Tree of Life.

Chaves G, Jardin C, Derst C, Musset B Biomolecules. 2023; 13(7).

PMID: 37509071 PMC: 10377628. DOI: 10.3390/biom13071035.

Role of voltage-gated proton channel (Hv1) in cancer biology.

Alvear-Arias J, Pena-Pichicoi A, Carrillo C, Fernandez M, Gonzalez T, Garate J Front Pharmacol. 2023; 14:1175702.

PMID: 37153807 PMC: 10157179. DOI: 10.3389/fphar.2023.1175702.

Unexpected expansion of the voltage-gated proton channel family.

Chaves G, Ayuyan A, Cherny V, Morgan D, Franzen A, Fieber L FEBS J. 2022; 290(4):1008-1026.

PMID: 36062330 PMC: 10911540. DOI: 10.1111/febs.16617.

Assessing Structural Determinants of Zn Binding to Human H1 via Multiple MD Simulations.

Jardin C, Chaves G, Musset B Biophys J. 2020; 118(5):1221-1233.

PMID: 31972155 PMC: 7063441. DOI: 10.1016/j.bpj.2019.12.035.

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