Zn2+-Binding to the Voltage-Gated Proton Channel Hv1/VSOP

Masayo Iwaki; Kohei Takeshita; Hiroko X Kondo; Kengo Kinoshita; Yasushi Okamura; Yu Takano; Atsushi Nakagawa; Hideki Kandori

doi:10.1021/acs.jpcb.8b04890

Zn²⁺-Binding to the Voltage-Gated Proton Channel Hv1/VSOP

J Phys Chem B. 2018 Oct 4;122(39):9076-9080. doi: 10.1021/acs.jpcb.8b04890. Epub 2018 Sep 25.

Authors

Masayo Iwaki, Kohei Takeshita, Hiroko X Kondo^{1

2}, Kengo Kinoshita^{3

4

5}, Yasushi Okamura, Yu Takano¹, Atsushi Nakagawa, Hideki Kandori

Affiliations

¹ Department of Biomedical Information Sciences, Graduate School of Information Sciences , Hiroshima City University , 3-4-1 Ozuka-Higashi , Asa-Minami-Ku, Hiroshima 731-3194 , Japan.
² Laboratory for Computational Molecular Design, RIKEN Center for Biosystems Dynamics Research , 6-2-3, Furuedai , Suita , 565-0874 , Japan.
³ Department of Applied Information Sciences, Graduate School of Information Sciences , Tohoku University , 6-3-09 Aramaki-Aza-Aoba , Aoba-ku, Sendai , 980-8579 , Japan.
⁴ Tohoku Medical Megabank Organization , Tohoku University , 2-1 Seityo-machi , Aoba-ku, Sendai , 980-8573 , Japan.
⁵ Institute of Development, Aging and Cancer , Tohoku University , 4-1 Seiryocho , Aoba-ku, Sendai , 980-8575 , Japan.

PMID: 30204443
DOI: 10.1021/acs.jpcb.8b04890

Abstract

The voltage-gated proton channel (Hv1/VSOP) is inhibited by Zn²⁺, of which the binding site is located in the extracellular region. We utilized attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to examine the coordination structure by monitoring protein structural changes induced by Zn²⁺-binding. The Zn²⁺-induced difference ATR-FTIR spectra of Hv1 showed IR features that can be assigned to the histidine C5-N1 and carboxylate-COO^- stretches as well as amide I changes likely in α-helical peptide bonds. Analysis of vibrational frequencies indicated that the Zn²⁺ is coordinated by the anionic carboxylate with monodentate mode and by the histidine at N1 (Nτ) position of the neutral imidazole form. Combined with quantum chemical calculations, the most probable coordination structure was proposed as a tetrahedral geometry with ligands of carboxylate and imidazole groups in addition to a water molecule.

Publication types

Research Support, Non-U.S. Gov't