Biology:HVCN1
From HandWiki
Voltage-gated hydrogen channel 1 is a protein that in humans is encoded by the HVCN1 gene.
Voltage-gated hydrogen channel 1 is a voltage-gated proton channel that has been shown to allow proton transport into phagosomes[1][2] and out of many types of cells including spermatozoa, electrically excitable cells and respiratory epithelial cells.[3] The proton-conducting HVCN1 channel has only transmembrane domains corresponding to the S1-S4 voltage sensing domains (VSD) of voltage-gated potassium channels and voltage-gated sodium channels.[4] Molecular simulation is consistent with a water-filled pore that can function as a "water wire" for allowing hydrogen bonded H+ to cross the membrane.[5][6] However, mutation of Asp112 in human Hv1 results in anion permeation, suggesting that obligatory protonation of Asp produces proton selectivity.[7] Quantum mechanical calculations show that the Asp-Arg interaction can produce proton selective permeation.[8] The HVCN1 protein has been shown to exist as a dimer with two functioning pores.[9][10] Like other VSD channels, HVCN1 channels conduct ions about 1000-fold slower than channels formed by tetrameric S5-S6 central pores.[11]
As a drug target
Small molecule inhibitors of the HVCN1 channel are being developed as chemotherapeutics and anti-inflammatory agents.[12]
References
- ↑ "Charge compensation during the phagocyte respiratory burst". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1757 (8): 996–1011. August 2006. doi:10.1016/j.bbabio.2006.01.005. PMID 16483534.
- ↑ "HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species". Nature Immunology 11 (3): 265–272. March 2010. doi:10.1038/ni.1843. PMID 20139987.
- ↑ "pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1". Trends in Cell Biology 21 (1): 20–28. January 2011. doi:10.1016/j.tcb.2010.09.006. PMID 20961760.
- ↑ "Functional reconstitution of purified human Hv1 H+ channels". Journal of Molecular Biology 387 (5): 1055–1060. April 2009. doi:10.1016/j.jmb.2009.02.034. PMID 19233200.
- ↑ "Water wires in atomistic models of the Hv1 proton channel". Biochimica et Biophysica Acta (BBA) - Biomembranes 1818 (2): 286–293. February 2012. doi:10.1016/j.bbamem.2011.07.045. PMID 21843503.
- ↑ "An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1". Nature Structural & Molecular Biology 17 (7): 869–875. July 2010. doi:10.1038/nsmb.1826. PMID 20543828.
- ↑ "Aspartate 112 is the selectivity filter of the human voltage-gated proton channel.". Nature 480 (7376): 273–277. 23 October 2011. doi:10.1038/nature10557. PMID 22020278. Bibcode: 2011Natur.480..273M.
- ↑ "Selectivity Mechanism of the Voltage-gated Proton Channel, HV1.". Scientific Reports 5. 8 May 2015. doi:10.1038/srep10320. PMID 25955978. Bibcode: 2015NatSR...510320D.
- ↑ "Strong cooperativity between subunits in voltage-gated proton channels". Nature Structural & Molecular Biology 17 (1): 51–56. January 2010. doi:10.1038/nsmb.1739. PMID 20023639.
- ↑ "The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity". Nature Structural & Molecular Biology 17 (1): 44–50. January 2010. doi:10.1038/nsmb.1738. PMID 20023640.
- ↑ "Voltage-gated proton channels: what's next?". The Journal of Physiology 586 (22): 5305–5324. November 2008. doi:10.1113/jphysiol.2008.161703. PMID 18801839.
- ↑ "Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains". Neuron 77 (2): 274–287. January 2013. doi:10.1016/j.neuron.2012.11.013. PMID 23352164.
Further reading
- "The role and structure of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1.". Journal of Biological Chemistry 285 (16): 12047–12054. Apr 2010. doi:10.1074/jbc.M109.040360. PMID 20147290.
- "Oligomerization of the voltage-gated proton channel.". Channels (Austin, Tex.) 4 (4): 260–265. 2010. doi:10.4161/chan.4.4.12789. PMID 20676047.
- "Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel.". Cell 140 (3): 327–337. Feb 2010. doi:10.1016/j.cell.2009.12.053. PMID 20144758.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Research 16 (1): 55–65. Jan 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes.". Journal of Biological Chemistry 285 (8): 5117–5121. Feb 2010. doi:10.1074/jbc.C109.082727. PMID 20037153.
- "Molecular and functional characterization of Hv1 proton channel in human granulocytes.". PLOS ONE 5 (11). Nov 2010. doi:10.1371/journal.pone.0014081. PMID 21124855. Bibcode: 2010PLoSO...514081P.
- "A voltage sensor-domain protein is a voltage-gated proton channel.". Science (New York, N.Y.) 312 (5773): 589–592. Apr 2006. doi:10.1126/science.1122352. PMID 16556803. Bibcode: 2006Sci...312..589S.
- "Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1.". Proceedings of the National Academy of Sciences of the United States of America 105 (22): 7692–7695. Jun 2008. doi:10.1073/pnas.0803277105. PMID 18509058. Bibcode: 2008PNAS..105.7692L.
- "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Research 14 (9): 1711–1718. Sep 2004. doi:10.1101/gr.2435604. PMID 15342556.
- "Expression, purification, crystallization and preliminary crystallographic study of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1.". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 65 (Pt 3): 279–281. Mar 2009. doi:10.1107/S1744309109003777. PMID 19255483.
- "Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function.". European Journal of Immunology 37 (11): 3197–3207. Nov 2007. doi:10.1002/eji.200737052. PMID 17948262.
- "Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T.". The Journal of General Physiology 136 (1): 35–46. Jul 2010. doi:10.1085/jgp.200910379. PMID 20548053.
- "Detailed comparison of expressed and native voltage-gated proton channel currents.". The Journal of Physiology 586 (10): 2477–2486. May 2008. doi:10.1113/jphysiol.2007.149427. PMID 18356202.
- "A voltage-gated proton-selective channel lacking the pore domain.". Nature 440 (7088): 1213–1216. Apr 2006. doi:10.1038/nature04700. PMID 16554753. Bibcode: 2006Natur.440.1213R.
- "Functionality of the voltage-gated proton channel truncated in S4.". Proceedings of the National Academy of Sciences of the United States of America 107 (5): 2313–2318. Feb 2010. doi:10.1073/pnas.0911868107. PMID 20018719. Bibcode: 2010PNAS..107.2313S.
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