전압 게이트형 수소 채널 1은 인간에서 HVCN1 유전자 에 의해 암호화 된 단백질이다.
전압 게이트형 수소 채널 1은 양성자가 정자조아 , 전기적 흥분성 세포 , 호흡기 상피 세포 등 여러 종류의 세포 중에서 파고솜 으로[5] [6] 게이트 양성자 채널 이다.[7] 양성자 전도 HVCN1 채널은 전압 게이트 칼륨 채널 과 전압 게이트 나트륨 채널 의 S1-S4 전압 감지 도메인(VSD)에 해당하는 전송 브레인 영역만 가지고 있다.[8] 분자시뮬레이션은 수소가 결합한 H가+ 막을 건널 수 있도록 하는 '물선 ' 기능을 할 수 있는 수분이 채워진 모공과 일치한다.[9] [10] 그러나 인간 Hv1에서 Asp112의 돌연변이는 음이온 투과로 나타나, Asp의 의무적인 양성자가 양성자 선택성을 생성한다는 것을 암시한다.[11] 양자역학적 계산에 따르면 아스프-아그 상호작용은 양성자 선택적 투과를 발생시킬 수 있다.[12] HVCN1 단백질은 두 개의 모공이 있는 조광기로서 존재하는 것으로 밝혀졌다.[13] [14] 다른 VSD 채널과 마찬가지로, HVCN1 채널은 사선형 S5-S6 중심 모공에 의해 형성된 채널보다 약 1000배 느리게 이온을 전도한다.[15]
마약 타겟으로 HVCN1 채널의 작은 분자 억제제는 화학요법 및 항염증제로 개발되고 있다.[16]
참조 ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000122986 - 앙상블 , 2017년 5월^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000064267 - 앙상블 , 2017년 5월^ "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" . Biochim. Biophys. Acta . 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, Dinsdale D, Pulford K, Khan M, Musset B, Cherny VV, Morgan D, Gascoyne RD, Vigorito E, DeCoursey TE, MacLennan IC, Dyer MJ (March 2010). "HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species" . Nat. Immunol . 11 (3): 265–72. 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 Cell Biol . 21 (1): 20–8. 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" . J. Mol. Biol . 387 (5): 1055–60. 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" . Biochim. Biophys. Acta . 1818 (2): 286–93. 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" . Nat. Struct. Mol. Biol . 17 (7): 869–75. 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): 273–7. doi :10.1038/nature10557 . PMC 3237871 PMID 22020278 . ^ Dudev, T; Musset, B; Morgan, D; Cherny, VV; Smith, SM; Mazmanian, K; DeCoursey, TE; Lim, C (8 May 2015). "Selectivity Mechanism of the Voltage-gated Proton Channel, HV1" . Scientific Reports . 5 : 10320. doi :10.1038/srep10320 . PMC 4429351 PMID 25955978 . ^ ^ 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" . Nat. Struct. Mol. Biol . 17 (1): 44–50. doi :10.1038/nsmb.1738 . PMC 2925041 PMID 20023640 . ^ DeCoursey TE (November 2008). "Voltage-gated proton channels: what's next?" . J. Physiol . 586 (Pt 22): 5305–24. 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): 274–87. doi :10.1016/j.neuron.2012.11.013 . PMC 3559007 PMID 23352164 .
추가 읽기 Li SJ, Zhao Q, Zhou Q, et al. (2010). "The role and structure of the carboxyl-terminal domain of the human voltage-gated proton channel Hv1" . J. Biol. Chem . 285 (16): 12047–54. doi :10.1074/jbc.M109.040360 PMC 2852942 PMID 20147290 . Musset B, Smith SM, Rajan S, et al. (2010). "Oligomerization of the voltage-gated proton channel" . Channels (Austin) . 4 (4): 260–5. doi :10.4161/chan.4.4.12789 . PMC 3025757 PMID 20676047 . Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y (2010). "Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel" . Cell . 140 (3): 327–37. doi :10.1016/j.cell.2009.12.053 PMID 20144758 . S2CID 7952753 . Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes" . Genome Res . 16 (1): 55–65. doi :10.1101/gr.4039406 . PMC 1356129 PMID 16344560 . Musset B, Capasso M, Cherny VV, et al. (2010). "Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes" . J. Biol. Chem . 285 (8): 5117–21. doi :10.1074/jbc.C109.082727 PMC 2820736 PMID 20037153 . Petheo GL, Orient A, Baráth M, et al. (2010). "Molecular and functional characterization of Hv1 proton channel in human granulocytes" . PLOS ONE . 5 (11): e14081. doi :10.1371/journal.pone.0014081 PMC 2990768 PMID 21124855 . Sasaki M, Takagi M, Okamura Y (2006). "A voltage sensor-domain protein is a voltage-gated proton channel". Science . 312 (5773): 589–92. doi :10.1126/science.1122352 . PMID 16556803 . S2CID 10259815 . Lee SY, Letts JA, Mackinnon R (2008). "Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1" . Proc. Natl. Acad. Sci. U.S.A . 105 (22): 7692–5. doi :10.1073/pnas.0803277105 PMC 2409406 PMID 18509058 . Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions" . Genome Res . 14 (9): 1711–8. doi :10.1101/gr.2435604 . PMC 515316 PMID 15342556 . Li SJ, Zhao Q, Zhou Q, Zhai Y (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 . 65 (Pt 3): 279–81. doi :10.1107/S1744309109003777 . PMC 2650464 PMID 19255483 . Suenaga T, Arase H, Yamasaki S, et al. (2007). "Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function" . Eur. J. Immunol . 37 (11): 3197–207. doi :10.1002/eji.200737052 PMID 17948262 . S2CID 25376411 . Iovannisci D, Illek B, Fischer H (2010). "Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T" . J. Gen. Physiol . 136 (1): 35–46. doi :10.1085/jgp.200910379 . PMC 2894549 PMID 20548053 . Clark HF, Gurney AL, Abaya E, et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment" . Genome Res . 13 (10): 2265–70. doi :10.1101/gr.1293003 . PMC 403697 PMID 12975309 . Musset B, Cherny VV, Morgan D, et al. (2008). "Detailed comparison of expressed and native voltage-gated proton channel currents" . J. Physiol . 586 (10): 2477–86. doi :10.1113/jphysiol.2007.149427 . PMC 2464343 PMID 18356202 . Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Ramsey IS, Moran MM, Chong JA, Clapham DE (2006). "A voltage-gated proton-selective channel lacking the pore domain" . Nature . 440 (7088): 1213–6. doi :10.1038/nature04700 . PMC 4084761 PMID 16554753 . Sakata S, Kurokawa T, Nørholm MH, et al. (2010). "Functionality of the voltage-gated proton channel truncated in S4" . Proc. Natl. Acad. Sci. U.S.A . 107 (5): 2313–8. doi :10.1073/pnas.0911868107 PMC 2836681 PMID 20018719 .
