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研究生:陳政彰
研究生(外文):Cheng-Chang Chen
論文名稱:雙層脂質膜內SARS冠狀病毒ORF8a蛋白組合以及HIV-1病毒Vpu蛋白與人類BST-2膜蛋白之組合
論文名稱(外文):Assemblies of ORF8a from SARS-CoV, and BST-2 with Vpu from HIV-1 within the lipid membrane
指導教授:費伍岡
指導教授(外文):Wolfgang B. Fischer
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生醫光電工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:60
中文關鍵詞:離子通道膜蛋白自我聚合
外文關鍵詞:ion channelmembrane proteinself-assembly
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  在許多的病毒基因中,帶有可以形成小型螺旋穿膜蛋白的基因編碼,這些蛋白質普遍擁有的功能是會影響宿主細胞膜的離子通透性或宿主細胞的某些細胞生物反應。這類的病毒膜蛋白通常是病毒繁衍感染必須的元素之一,因此近年來也在對抗病毒的各種治療研究中受到高度的關注。自我聚合(self-assemble)的反應是使這類蛋白質能夠具有細胞生物功能的重要機制之一。

  在第一部分的論文中,針對人類急性呼吸道症候群冠狀病毒的結構蛋白之一的開放式讀架(open reading frame) 8a膜蛋白進行研究。ORF8a膜蛋白全序列為三十九個胺基酸所排列組成,其中包含一段單一的穿膜區域。本實驗所使用的全序列純膜蛋白由胜固相合成法所製成。實驗中發現,當它在人工合成的雙層脂質膜中重組後會形成一個具有陽離子選擇性的陽離子通道。由膜電位電生理的實驗記錄顯示,ORF8a蛋白在攝氏三十八點五度的環境中可以展現一個主要導電性大約8.5 pS (pico-sieman) 的離子通道活性。在電腦模擬的研究方面,ORF8a蛋白其中的二十二個胺基酸長度的穿膜部分被假設為理想的單體螺旋結構單位,藉由此單體螺旋建立起排列成束的結構模型並將其嵌置於高度水合之POPC雙層脂質細胞膜之中,俾以進一步研究取得更多蛋白結構的資訊。根據電腦模擬的結果指出,ORF8a蛋白有可能是由五個相同的單體螺旋結構單位所聚合的離子通道。

  在第二部分的論文,則是針對來自後天免疫不全症候群病毒之Vpu蛋白與人類免疫細胞之BST-2蛋白的穿膜部分進行研究,評估他們胺基酸排列組成的結構與潛在可能的互動聚合模式。本實驗乃使用人類之BST-2蛋白與非人類之靈長類動物之BST-2蛋白來進行比較,其中包含在非人靈長類動物之BST-2蛋白序列穿膜位置中插入白胺酸與甘胺酸的擬人化之非人類靈長動物BST-2蛋白。藉由流式細胞儀的實驗結果,不但重複證實Vpu蛋白會影響人類BST-2蛋白在人體宿主細胞膜上的表現,另外還發現在穿膜區域序列中嵌入白胺酸與甘胺酸的擬人化之恆河猴BST-2蛋白不僅會受到Vpu的抑制調控,還會使BST-2的表現量減少。這些實驗結果暗示著BST-2與Vpu互動的關鍵因素可能來自穿膜蛋白的區域。此外在此論文中也展示了利用電腦模擬方法來研究人類BST-2與突變Vpu蛋白之穿膜部分的互動結構模型。
  Many genomes of viruses encode small membrane spanning proteins which are proposed to alter membrane permeability or cell response. These membrane proteins are getting into the focus for antiviral therapy since they are essential for some of the viruses. One of the common themes of the mechanism of function of the proteins is to self-assemble to form the functional form.

  In the first part of this study, the open reading frame (ORF) 8a membrane protein encoded in structural region of Human Severe Acute Respiratory Syndrome Coronavirus is investigated. The full length ORF8a protein is 39 residues long and contains a single transmembrane domain. Full length protein is synthesized using solid phase peptide synthesis. When reconstituted into artificial lipid bilayers it forms cation-selective ion channels. The bilayer recordings show ion channel activity with a main conductance level of around 8.5 pS also at elevated temperatures (38.5°C). In silico studies with a 22 amino acid transmembrane (TM) domain are done to assess conformational space of the monomeric ORF8a helix. With this monomeric helix homooligomeric helical bundle models are built and embedded in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycerol-3 -phosphatidylcholine bilayer. Results of computational modeling suggest that SARS ORF8a could form a pentameric pore.

  The second part of this study focuses on the evaluation of amino acids within the TM domains (TMDs) of Vpu and BST-2 and their role in the putative assembly process. The human and non-human primates BST-2 TMDs, including the LG-insertion mutant, are compared. Data from flow cytometry assays of Vpu-mediated modulation of BST-2 are presented. The data illustrate that the L29G30 TMD mutant of Rhesus BST-2 is down regulated from the cell surface by Vpu and also expressed at a lower level than other BST2 types. These results imply that an interaction between TMDs of BST-2 and Vpu should exist. We also have started to model the interaction of the TMDs of BST-2 and Vpu mutant (A18H) using computational methods.
Content
Acknowledgment 3
Abstract 5
論文摘要 7
Introduction: 9
Assembly of homooligomers, e.g. SARS-ORF8a 10
Assembly of heteroligomers, e.g. BST-2 and Vpu 12
Materials and methods: 13
ORF8a peptide synthesis 13
Reconstitution and channel recordings of ORF8a 13
Flow Cytometry for BST-2 14
Computational Methods 14
Results: 19
Homooligomeric helices of ORF8a peptide 19
Transmembrane Domain of ORF8a 19
Channel recording of ORF8a 20
MD simulations of ORF8a 25
Heteroligomeric helices of Vpu from HIV-1 with host vector BST-2 32
Transmembrane domains of Vpu and BST-2 32
Vpu mediated downregulation of Human BST-2 and L29G30 insertion mutant non-primate BST-2 33
MD simulation of TMDs of BST-2 and Vpu 37
Assembly of TMDs of BST-2 and Vpu 41
Discussion: 44
Computational results: 44
Interactions of Transmembrane Domains of BST-2 and Vpu 45
Conclusion 46
Reference 48
Reference
1. Gonzales, M. E., and L. Carrasco. 2003. Viroporins. FEBS Lett. 552:28-34.
2. Fischer, W. B., editor. 2005. Viral membrane proteins: structure, function and drug design. Kluwer Academic / Plenum Publisher, New York.
3. Krüger, J., and W. B. Fischer. 2008. Exploring the conformational space of Vpu from HIV-1: a versatile and adaptable protein. J. Comp. Chem. 29:2416-2424.
4. Pinto, L. H., L. J. Holsinger, and R. A. Lamb. 1992. Influenza virus M2 protein has ion channel activity. Cell 69:12.
5. Chizhmakov, I. V., F. M. Geraghty, D. C. Ogden, A. Hayhurst, M. Antoniou, and A. J. Hay. 1996. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. J. Physiology. 494:8.
6. Lin, C., B. D. Lindenbach, B. M. Pragai, D. W. McCourt, and C. M. Rice. 1994. Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J. Virol. 68:5063-5073.
7. Lu, W., B. J. Zheng, K. Xu, W. Schwarz, L. Du, C. K. L. Wong, J. Chen, S. Duan, V. Deubel, and B. Sun. 2006. Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release. PNAS 103:6.
8. Strebel, K., T. Klimkait, and M. A. Martin. 1988. Novel gene of HIV-1, vpu, and its 16-kilodalton product. Science 241:1221-1223.
9. Cohen, E. A., E. F. Terwilliger, J. G. Sodroski, and W. A. Haseltine. 1988. Identification of a protein encoded by the vpu gene of HIV-1. Nature 334:532-534.
10. Stouffer, A. L., R. Acharya, D. Salom, A. S. Levine, L. Di Constanzo, C. S. Soto, V. Tereshko, V. Nanda, S. Stayrook, and W. F. DeGrado. 2008. Structural basis for the function and inhibition of an influenza virus proton channel. Nature 451:596-599.
11. Schnell, J. R., and J. J. Chou. 2008. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 451:591-595.
12. Kovacs, F. A., and T. A. Cross. 1997. Transmembrane four-helix bundle of influenza A M2 protein channel: structural implications from helix tilt and orientation. Biophys. J. 73:2511-2517.
13. Henklein, P., R. Kinder, U. Schubert, and B. Bechinger. 2000. Membrane interactions and alignment of structures within the HIV-1 Vpu cytoplasmic domain: effect of phosphorylation of serines 52 and 56. FEBS Lett. 482:220-224.
14. Park, S. H., A. A. Mrse, A. A. Nevzorov, M. F. Mesleh, M. Oblatt-Montal, M. Montal, and S. J. Opella. 2003. Three-dimensional structure of the channel-forming trans-membrane domain of virus protein "u" (Vpu) from HIV-1. J. Mol. Biol. 333:409-424.
15. Duff, K. C., S. M. Kelly, N. C. Price, and J. P. Bradshaw. 1992. The secondary structure of influenza A M2 transmembrane domain. A circular dichroism study. FEBS Lett. 311:256-258.
16. Kukol, A., and I. T. Arkin. 1999. Vpu transmembrane peptide structure obtained by site-specific fourier transform infrared dichroism and global molecular dynamics searching. Biophys. J. 77:1594-1601.
17. Kukol, A., P. D. Adams, L. M. Rice, A. T. Brunger, and I. T. Arkin. 1999. Experimentally based orientational refinement of membrane protein models: a structure for the influenza A M2 H+ channel. J. Mol. Biol. 286:951-962.
18. Bu, L., W. Im, and C. L. Brooks III. 2007. Membrane assembly of simple helix homo-oligomers studied via molecular dynamics simulations. Biophys. J. 92:854-863.
19. Grice, A. L., I. D. Kerr, and M. S. P. Sansom. 1997. Ion channels formed by HIV-1 Vpu: a modelling and simulation study. FEBS Lett. 405:299-304.
20. Cordes, F., A. Kukol, L. R. Forrest, I. T. Arkin, M. S. P. Sansom, and W. B. Fischer. 2001. The structure of the HIV-1 Vpu ion channel: modelling and simulation studies. Biochim. Biophys. Acta 1512:291-298.
21. Patargias, G., N. Zitzmann, R. Dwek, and W. B. Fischer. 2006. Protein-protein interactions: modeling the hepatitis C virus ion channel p7. J. Med. Chem. 49:648-655.
22. Kokubo, H., and Y. Okamoto. 2004. Self-assembly of transmembrane helices of bacteriorhodopsin by replica-exchange Monte Carlo simulation. Chem. Phys. Lett. 392:168-175.
23. Kokubo, H., and Y. Okamoto. 2004. Prediction of membrane protein structures by replica exchange Monte Carlo simulations: case of two helices. J. Chem. Phys. 120:10837-10847.
24. Park, Y., M. Elsner, R. Staritzbichler, and V. Helms. 2004. Novel scoring function for modeling structures of oligomers of transmembrane a-helices. Proteins 57:577-585.
25. Kim, S., A. K. Chamberlain, and J. U. Bowie. 2004. Membrane channel structure of Heliobacter pylori vacuolating toxin: role of multiple GXXG motifs in cylindrical channels. Proc. Natl. Acad. Sci. USA 101:5988-5991.
26. Hessa, T., H. Kim, K. Bihlmaier, C. Lundin, J. Boekel, H. Andersson, I. Nilsson, S. H. White, and G. von Heijne. 2005. Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 433:377-381.
27. Popot, J.-L., and D. M. Engelman. 1990. Membrane protein folding and oligomerization: the two-stage model. Biochemistry 29:4031-4037.
28. Engelman, D. M., Y. Chen, C.-N. Chin, A. R. Curran, A. M. Dixon, A. D. Dupuy, A. S. Lee, U. Lehnert, E. E. Matthews, Y. K. Reshetnyak, A. Senes, and J.-L. Popot. 2003. Membrane protein folding: beyond the two stage model. FEBS Lett. 555:122-125.
29. Konrad Stadler, V. M., Markus Eickmann, Stephan Becker, Sergio Abrignani, Hans-Dieter Klenk and Rino Rappuoli. 2003. SARS — BEGINNING TO UNDERSTAND A NEW VIRUS. NATURE REVIEWS | MICROBIOLOGY 1:10.
30. Ksiazek TG, E. D., Goldsmith CS, et al. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348:14.
31. 2004. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 World Health Organization.
32. 2004. Preliminary clinical description of severe acute respiratory syndrome. World Health Organization.
33. J . Peiris , S. L., L . Poon , Y . Guan , L . Yam , W . Lim , J . Nicholls , W . Yee , W . Yan , M . Cheung. 2003. Coronavirus as a possible cause of severe acute respiratory syndrome. The Lancet 361:7.
34. Stadler, K., V. Masignani, M. Eickmann, S. Becker, S. Abrignani, H.-D. Klenk, and R. Rappuoli. 2003. SARS — BEGINNING TO UNDERSTAND A NEW VIRUS. NATURE REVIEWS | MICROBIOLOGY 1:10.
35. Ksiazek, T. G., D. Erdman, C. S. Goldsmith, and e. al. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348:14.
36. Marra, M. A., S. J. M. Jones, C. R. Astell, R. A. Holt, A. Brooks-Wilson, Y. S. N. Butterfield, J. Khattra, J. K. Asano, S. A. Barber, S. Y. Chan, A. Cloutier, S. M. Coughlin, D. Freeman, N. Girn, O. L. Griffith, S. R. Leach, M. Mayo, H. McDonald, S. B. Montgomery, P. K. Pandoh, A. S. Petrescu, A. G. Robertson, J. E. Schein, A. Siddiqui, D. E. Smailus, J. M. Stott, G. S. Yang, F. Plummer, A. Andonov, H. Artsob, N. Bastien, K. Bernard, T. F. Booth, D. Bowness, M. Czub, M. Drebot, L. Fernando, R. Flick, M. Garbutt, M. Gray, A. Grolla, S. Jones, H. Feldmann, A. Meyers, A. Kabani, Y. Li, S. Normand, U. Stroher, G. A. Tipples, S. Tyler, R. Vogrig, D. Ward, B. Watson, R. C. Brunham, M. Krajden, M. Petric, D. M. Skowronski, C. Upton, and R. L. Roper. 2003. The Genome Sequence of the SARS-Associated Coronavirus. Science 300:7.
37. Rota, P. A., and e. al. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:6.
38. Zeng, F. Y., and e. al. 2003. The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39). Exp. Biol. Med. 228:8.
39. Guan, Y., B. J. Zheng, Y. Q. He, X. L. Liu, Z. X. Zhuang, C. L. Cheung, S. W. Luo, P. H. Li, L. J. Zhang, Y. J. Guan, K. M. Butt, K. L. Wong, K. W. Chan, W. Lim, K. F. Shortridge, K. Y. Yuen, J. S. M. Peiris, and L. L. M. Poon. 2003. Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China. Science 302:4.
40. Chen, C. Y., Y. H. Ping, H. C. Lee, K. H. Chen, Y. M. Lee, Y. J. Chan, T. C. Lien, T. S. Jap, C. H. Lin, L. S. Kao, and Y. M. A. Chen. 2007. Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis. The Journal of Infectious Diseases 196:11.
41. Montal, M. 2003. Structure-function correlates of Vpu, a membrane protein of HIV-1. FEBS Lett. 552:47-53.
42. Chen, M.-Y., F. Maldarelli, M. A. Martin, and K. Strebel. 1993. Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: The cytoplasmic domain contributes to Vpu sensitivity. J. Virol. 67:3877-3884.
43. Friborg, J., A. Ladha, H. Göttlinger, W. A. Haseltine, and E. A. Cohen. 1995. Functional analysis of the phospholrylation sites on the Human Immunodeficiency Virus Type-1 Vpu protein. J. Acc. Im. Def. Syn. Hum. Retr. 8:10-22.
44. Margottin, F., S. Benichou, H. Durand, V. Richard, L. X. Liu, and R. Benarous. 1996. Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: Role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation. Virology 223:381-386.
45. Schubert, U., S. Bour, A. V. Ferrer-Montiel, M. Montal, F. Maldarelli, and K. Strebel. 1996. The two biological activities of human immunodeficiency virus type 1 Vpu protein involve two separable structural domains. J. Virol. 70:809-819.
46. Hsu, K., J. Seharaseyon, P. Dong, S. Bour, and E. Marbán. 2004. Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Molec. Cell 14:259-267.
47. Neil, S. J. D., T. Zang, and P. D. Bieniasz. 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:6.
48. Van Damme, N., D. Goff, C. Katsura, R. L. Jorgenson, R. Mitchell, M. C. Johnson, E. B. Stephens, and J. Guatelli. 2008. The Interferon-Induced Protein BST-2 Restricts HIV-1 Release and Is Downregulated from the Cell Surface by the Viral Vpu Protein. Cell Host & Microbe 3:8.
49. Fischer, W. B. 2003. Vpu from HIV-1 on an atomic scale: experiments and computer simulations. FEBS 552:8.
50. Krüger, J., and W. B. Fischer. 2009. Assembly of viral membrane proteins. Submitted.
51. Mehnert, T., Y. H. Lam, P. J. Judge, A. Routh, D. Fischer, A. Watts, and W. B. Fischer. 2007. Towards a mechanism of function of the viral ion channel Vpu from HIV-1. J. Biomol. Struct. Dyn. 24:589-596.
52. M. Cserzo, E. W., I. Simon, G. von Heijne and A. Elofsson. 1997. Prediction of transmembrane alpha-helices in procariotic membrane proteins: the Dense Alignment Surface method. Prot. Eng. 10:4.
53. S. Moller, M. D. R. C., R. Apweiler. 2001. Evaluation of methods for the prediction of membrane spanning regions. Bioinformatics 17:8.
54. E. L.L. Sonnhammer, G. v. H., A. Krogh. 1998. A hidden Markov model for predicting transmembrane helices in protein sequences. Proceedings of the Sixth International Conference on Intelligent Systems for Molecular Biology:8.
55. A. Krogh, B. L., G. von Heijne, and E. L. L. Sonnhammer. 2001. Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. Journal of Molecular Biology 305:14.
56. Hofmann, K., and W. Stoffel. 1993. TMbase - A database of membrane spanning proteins segments. Biochemistry 374:1.
57. Juretic, D., Zoranic, L., Zucic, D. 2002. Basic charge clusters and predictions of membrane protein topology. J. Chem. Inf. Comput. 42:13.
58. Hirokawa T., B.-C. S., and Mitaku S. 1998. SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics 14:2.
59. Mitaku S., H. T. 1999. Physicochemical factors for discriminating between soluble and membrane proteins: hydrophobicity of helical segments and protein length. Prot. Eng. 12:5.
60. Mitaku S., H. T., and Tsuji T. 2002. Amphiphilicity index of polar amino acids as an aid in the characterization of amino acid preference at membrane-water interfaces. Bioinformatics 18:9.
61. Engh, R. A., and R. Huber. 1991. Accurate bond and angle parameters for X-ray protein structure refinement. Acta Cryst. A47:9.
62. Kupzig, S., V. Korolchuk, R. Rollason, A. Sugden, A. Wilde, and G. Banting. 2003. Bst-2/HM1.24 Is a Raft-Associated Apical Membrane Protein with an Unusual Topology. Traffic 4:16.
63. Engh, R. A., and R. Huber. 1991. Accurate bond and angle parameter for X-ray protein-structure refinement. Acta Crystallogr. A 47.
64. Faham, S., D. Yang, E. Bare, S. Yohannan, J. P. Whitelegge, and J. U. Bowie. 2004. Side-chain contributions to membrane protein structure and stability. J. Mol. Biol. 335:297-305.
65. Bowie, J. U. 2005. Solving the membrane protein folding problem. Nature 438:581-589.
66. Cordes, F. S., A. Tustian, M. S. P. Sansom, A. Watts, and W. B. Fischer. 2002. Bundles consisting of extended transmembrane segments of Vpu from HIV-1: computer simulations and conductance measurements. Biochemistry 41:7359-7365.
67. Patargias, G., H. Martay, and W. B. Fischer. 2009. Reconstructing potentials of mean force from short steered molecular dynamics simulations of Vpu from HIV-1. J. Biomol. Struc. Dyn. 26:1-12.
68. Leonard, R. J., C. G. Labarca, P. Charnet, N. Davidson, and H. A. Lester. 1988. Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science 242:1578-1581.
69. Revah, F., J. L. Galzi, J. Giraudat, P. Y. Haumont, F. Lederer, and J. P. Changeux. 1990. The noncompetitive blocker [3H]chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: implications for the alpha-helical organization of regions M2 and for the structure of the ion channel. PNAS USA 87:4675-4679.
70. Oiki, S., V. Madison, and M. Montal. 1990. Bundles of amphipathic trasnmembrane a-helices as a structural motif for ion-conducting channel proteins: studies on sodium channels and acetylcholine receptors. Proteins 8:226-236.
71. Fischer, W. B., and M. S. P. Sansom. 2002. Viral ion channels: structure and function. Biochim. Biophys. Acta 1561:27-45.
72. Melton, J. V., G. D. Ewart, R. C. Weir, P. G. Board, E. Lee, and P. W. Gage. 2002. Alphavirus 6K proteins form ion channels. J. Biol. Chem. 277:46923-46931.
73. Mehnert, T., A. Routh, P. J. Judge, Y. H. Lam, D. Fischer, A. Watts, and W. B. Fischer. 2008. Biophysical characterisation of Vpu from HIV-1 suggests a channel-pore dualism. Proteins 70:1488-1497.
74. Slugoski, M. D., A. M. L. Ng, S. Y. M. Yao, K. M. Smith, C. C. Lin, J. Zhang, E. Karpinski, C. E. Cass, S. A. Baldwin, and J. D. Young. 2008. A proton-mediated conformational shift identifies a mobile pore-lining cysteine residue (Cys-561) in human concentrative nucleoside transporter 3. J. Biol. Chem. 283:8496-8507.
75. Mei, Z.-Z., H.-J. Mao, and L.-H. Jiang. 2006. Conserved cysteine residues in the pore region are obligatory for human TRPM2 channel function. Am. J. Physiol. Cell Physiol. 291:C1022-C1028.
76. Kuner, T., C. Beck, B. Sakmann, and P. H. Seeburg. 2001. Channel-lining residues of the AMPA receptor M2 segment: structural environment of the Q/R site and identification of the selectivity filter. J. Neurosci. 21:4162-4172.
77. Schubert, U., L. C. Antón, I. Baík, J. H. Cox, S. Bour, J. R. Bennink, M. Orlowski, K. Strebel, and J. W. Yewdell. 1998. CD4 Glycoprotein Degradation Induced by Human Immunodeficiency Virus Type 1 Vpu Protein Requires the Function of Proteasomes and the Ubiquitin-Conjugating Pathway Journal of Virology 72:9.
78. Margottin, F., S. P. Bour, H. Durand, L. Selig, S. Benichou, V. Richard, D. Thomas, K. Strebel, and R. Benarous. 1998. A Novel Human WD Protein, h-βTrCP, that Interacts with HIV-1 Vpu Connects CD4 to the ER Degradation Pathway through an F-Box Motif Molecular Cell 1:9.
79. Fischer, W. B. 2003. Vpu from HIV-1 on an atomic scale: experiments and computer simulations. FEBS Lett. 552:39-46.
80. Schubert, U., A. V. Ferrer-Montiel, M. Oblatt-Montal, P. Henklein, K. Strebel, and M. Montal. 1996. Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells. FEBS Lett. 398:12-18.
81. Vidal-Lalienaa, M., X. Romeroa, S. Marcha, V. Requenaa, J. Petrizb, and P. Engel. 2005. Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry. Cellular immunology 236:10.
82. Bartee, E., A. McCormack, and K. Früh. 2006. Quantitative Membrane Proteomics Reveals New Cellular Targets of Viral Immune Modulators. PLoS Pathog 2.
83. Ohtomo, T., Y. Sugamata, Y. Ozaki, K. Ono, Y. Yoshimura, S. Kawai, Y. Koishihara, S. Ozaki, M. Kosaka, T. Hirano, and M. Tsuchiyaa. 1999. Molecular Cloning and Characterization of a Surface Antigen Preferentially Overexpressed on Multiple Myeloma Cells. Biochemical and Biophysical Research Communicatons 258:8.
84. Hout, D. R., L. M. Gomez, E. Pacyniak, J.-M. Millera, M. S. Hill, and E. B. Stephens. 2006. A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian–human immunodeficiency virus (SHIVKU-1bMC33) susceptible to rimantadine Virology 348:13.
85. Park, S. H., and S. J. Opella. 2007. Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu : Implications for HIV-1 susceptibility to channel blocking drugs. Protein science 16:11.
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