Nuclear Magnetic Resonance Solution Structure and Functional Behavior of the Human Proton Channel
- PMID: 31365236
- DOI: 10.1021/acs.biochem.9b00471
Nuclear Magnetic Resonance Solution Structure and Functional Behavior of the Human Proton Channel
Abstract
The human voltage-gated proton channel [Hv1(1) or VSDO(2)] plays an important role in the human innate immune system. Its structure differs considerably from those of other cation channels. It is built solely of a voltage-sensing domain and thus lacks the central pore domain, which is essential for other cation channels. Here, we determined the solution structure of an N- and C-terminally truncated human Hv1 (Δ-Hv1) in the resting state by nuclear magnetic resonance (NMR) spectroscopy. Δ-Hv1 comprises the typical voltage-sensing antiparallel four-helix bundle (S1-S4) preceded by an amphipathic helix (S0). The solution structure corresponds to an intermediate state between resting and activated forms of voltage-sensing domains. Furthermore, Zn2+-induced closing of proton channel Δ-Hv1 was studied with two-dimensional NMR spectroscopy, which showed that characteristic large scale dynamics of open Δ-Hv1 are absent in the closed state of the channel. Additionally, pH titration studies demonstrated that a higher H+ concentration is required for the protonation of side chains in the Zn2+-induced closed state than in the open state. These observations demonstrate both structural and dynamical changes involved in the process of voltage gating of the Hv1 channel and, in the future, may help to explain the unique properties of unidirectional conductance and the exceptional ion selectivity of the channel.
Similar articles
-
X-ray crystal structure of voltage-gated proton channel.Nat Struct Mol Biol. 2014 Apr;21(4):352-7. doi: 10.1038/nsmb.2783. Epub 2014 Mar 2. Nat Struct Mol Biol. 2014. PMID: 24584463
-
Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations.Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13490-13498. doi: 10.1073/pnas.1920943117. Epub 2020 May 27. Proc Natl Acad Sci U S A. 2020. PMID: 32461356 Free PMC article.
-
Mapping of sites facing aqueous environment of voltage-gated proton channel at resting state: a study with PEGylation protection.Biochim Biophys Acta. 2014 Jan;1838(1 Pt B):382-7. doi: 10.1016/j.bbamem.2013.10.001. Epub 2013 Oct 16. Biochim Biophys Acta. 2014. PMID: 24140009
-
Gating mechanisms of voltage-gated proton channels.Annu Rev Biochem. 2015;84:685-709. doi: 10.1146/annurev-biochem-060614-034307. Annu Rev Biochem. 2015. PMID: 26034892 Review.
-
Voltage-gated proton (H(v)1) channels, a singular voltage sensing domain.FEBS Lett. 2015 Nov 14;589(22):3471-8. doi: 10.1016/j.febslet.2015.08.003. Epub 2015 Aug 18. FEBS Lett. 2015. PMID: 26296320 Review.
Cited by
-
Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proc Natl Acad Sci U S A. 2024 Sep 17;121(38):e2407479121. doi: 10.1073/pnas.2407479121. Epub 2024 Sep 11. Proc Natl Acad Sci U S A. 2024. PMID: 39259593
-
Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects.Cell Res. 2022 May;32(5):461-476. doi: 10.1038/s41422-022-00616-y. Epub 2022 Feb 3. Cell Res. 2022. PMID: 35115667 Free PMC article.
-
Mechanically-primed voltage-gated proton channels from angiosperm plants.Nat Commun. 2023 Nov 18;14(1):7515. doi: 10.1038/s41467-023-43280-5. Nat Commun. 2023. PMID: 37980353 Free PMC article.
-
Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state.Elife. 2020 Feb 25;9:e53901. doi: 10.7554/eLife.53901. Elife. 2020. PMID: 32096762 Free PMC article.
-
Role of voltage-gated proton channel (Hv1) in cancer biology.Front Pharmacol. 2023 Apr 20;14:1175702. doi: 10.3389/fphar.2023.1175702. eCollection 2023. Front Pharmacol. 2023. PMID: 37153807 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
