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HVCN1
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| HVCN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | HVCN1, HV1, VSOP, hydrogen voltage gated channel 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 611227; MGI: 1921346; HomoloGene: 12535; GeneCards: HVCN1; OMA:HVCN1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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[5][6] and out of many types of cells including spermatozoa, electrically excitable cells and respiratory epithelial cells.[7] 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.[8] 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.[9][10] However, mutation of Asp112 in human Hv1 results in anion permeation, suggesting that obligatory protonation of Asp produces proton selectivity.[11] Quantum mechanical calculations show that the Asp-Arg interaction can produce proton selective permeation.[12] The HVCN1 protein has been shown to exist as a dimer with two functioning pores.[13][14] Like other VSD channels, HVCN1 channels conduct ions about 1000-fold slower than channels formed by tetrameric S5-S6 central pores.[15]
As a drug target
[edit]Small molecule inhibitors of the HVCN1 channel are being developed as chemotherapeutics and anti-inflammatory agents.[16]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000122986 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064267 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Murphy R, DeCoursey TE (August 2006). "Charge compensation during the phagocyte respiratory burst". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1757 (8): 996–1011. doi:10.1016/j.bbabio.2006.01.005. PMID 16483534.
- ^ Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C, Cain K, et al. (March 2010). "HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species". Nature Immunology. 11 (3): 265–272. doi:10.1038/ni.1843. PMC 3030552. PMID 20139987.
- ^ Capasso M, DeCoursey TE, Dyer MJ (January 2011). "pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1". Trends in Cell Biology. 21 (1): 20–28. doi:10.1016/j.tcb.2010.09.006. PMC 3014425. PMID 20961760.
- ^ Lee SY, Letts JA, MacKinnon R (April 2009). "Functional reconstitution of purified human Hv1 H+ channels". Journal of Molecular Biology. 387 (5): 1055–1060. doi:10.1016/j.jmb.2009.02.034. PMC 2778278. PMID 19233200.
- ^ Wood ML, Schow EV, Freites JA, White SH, Tombola F, Tobias DJ (February 2012). "Water wires in atomistic models of the Hv1 proton channel". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1818 (2): 286–293. doi:10.1016/j.bbamem.2011.07.045. PMC 3245885. PMID 21843503.
- ^ Ramsey IS, Mokrab Y, Carvacho I, Sands ZA, Sansom MS, Clapham DE (July 2010). "An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1". Nature Structural & Molecular Biology. 17 (7): 869–875. doi:10.1038/nsmb.1826. PMC 4035905. PMID 20543828.
- ^ Musset B, Smith SM, Rajan S, Morgan D, Cherny VV, Decoursey TE (23 October 2011). "Aspartate 112 is the selectivity filter of the human voltage-gated proton channel". Nature. 480 (7376): 273–277. Bibcode:2011Natur.480..273M. doi:10.1038/nature10557. PMC 3237871. PMID 22020278.
- ^ Dudev T, Musset B, Morgan D, Cherny VV, Smith SM, Mazmanian K, et al. (8 May 2015). "Selectivity Mechanism of the Voltage-gated Proton Channel, HV1". Scientific Reports. 5 10320. Bibcode:2015NatSR...510320D. doi:10.1038/srep10320. PMC 4429351. PMID 25955978.
- ^ Gonzalez C, Koch HP, Drum BM, Larsson HP (January 2010). "Strong cooperativity between subunits in voltage-gated proton channels". Nature Structural & Molecular Biology. 17 (1): 51–56. doi:10.1038/nsmb.1739. PMC 2935852. PMID 20023639.
- ^ Tombola F, Ulbrich MH, Kohout SC, Isacoff EY (January 2010). "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. doi:10.1038/nsmb.1738. PMC 2925041. PMID 20023640.
- ^ DeCoursey TE (November 2008). "Voltage-gated proton channels: what's next?". The Journal of Physiology. 586 (22): 5305–5324. doi:10.1113/jphysiol.2008.161703. PMC 2655391. PMID 18801839.
- ^ Hong L, Pathak MM, Kim IH, Ta D, Tombola F (January 2013). "Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains". Neuron. 77 (2): 274–287. doi:10.1016/j.neuron.2012.11.013. PMC 3559007. PMID 23352164.
Further reading
[edit]- Li SJ, Zhao Q, Zhou Q, Unno H, Zhai Y, Sun F (Apr 2010). "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. doi:10.1074/jbc.M109.040360. PMC 2852942. PMID 20147290.
- Musset B, Smith SM, Rajan S, Cherny VV, Morgan D, DeCoursey TE (2010). "Oligomerization of the voltage-gated proton channel". Channels. 4 (4). Austin, Tex.: 260–265. doi:10.4161/chan.4.4.12789. PMC 3025757. PMID 20676047.
- Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y (Feb 2010). "Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel". Cell. 140 (3): 327–337. doi:10.1016/j.cell.2009.12.053. PMID 20144758. S2CID 7952753.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Musset B, Capasso M, Cherny VV, Morgan D, Bhamrah M, Dyer MJ, et al. (Feb 2010). "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. doi:10.1074/jbc.C109.082727. PMC 2820736. PMID 20037153.
- Petheo GL, Orient A, Barath M, Kovacs I, Rethi B, Lanyi A, et al. (Nov 2010). "Molecular and functional characterization of Hv1 proton channel in human granulocytes". PLOS ONE. 5 (11) e14081. Bibcode:2010PLoSO...514081P. doi:10.1371/journal.pone.0014081. PMC 2990768. PMID 21124855.
- Sasaki M, Takagi M, Okamura Y (Apr 2006). "A voltage sensor-domain protein is a voltage-gated proton channel". Science. 312 (5773). New York, N.Y.: 589–592. Bibcode:2006Sci...312..589S. doi:10.1126/science.1122352. PMID 16556803. S2CID 10259815.
- Lee SY, Letts JA, Mackinnon R (Jun 2008). "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. Bibcode:2008PNAS..105.7692L. doi:10.1073/pnas.0803277105. PMC 2409406. PMID 18509058.
- Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (Sep 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–1718. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
- Li SJ, Zhao Q, Zhou Q, Zhai Y (Mar 2009). "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. doi:10.1107/S1744309109003777. PMC 2650464. PMID 19255483.
- Suenaga T, Arase H, Yamasaki S, Kohno M, Yokosuka T, Takeuchi A, et al. (Nov 2007). "Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function". European Journal of Immunology. 37 (11): 3197–3207. doi:10.1002/eji.200737052. PMID 17948262. S2CID 25376411.
- Iovannisci D, Illek B, Fischer H (Jul 2010). "Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T". The Journal of General Physiology. 136 (1): 35–46. doi:10.1085/jgp.200910379. PMC 2894549. PMID 20548053.
- Musset B, Cherny VV, Morgan D, Okamura Y, Ramsey IS, Clapham DE, et al. (May 2008). "Detailed comparison of expressed and native voltage-gated proton channel currents". The Journal of Physiology. 586 (10): 2477–2486. doi:10.1113/jphysiol.2007.149427. PMC 2464343. PMID 18356202.
- Ramsey IS, Moran MM, Chong JA, Clapham DE (Apr 2006). "A voltage-gated proton-selective channel lacking the pore domain". Nature. 440 (7088): 1213–1216. Bibcode:2006Natur.440.1213R. doi:10.1038/nature04700. PMC 4084761. PMID 16554753.
- Sakata S, Kurokawa T, Norholm MH, Takagi M, Okochi Y, Heijne G, et al. (Feb 2010). "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. Bibcode:2010PNAS..107.2313S. doi:10.1073/pnas.0911868107. PMC 2836681. PMID 20018719.