Structure and immunogenicity of a peptide vaccine, including the complete HIV-1 gp41 2F5 epitope: Implications for antibody recognition mechanism and immunogen design

Journal of Biological Chemistry

Volumn 289, Issue 10, 2014, Pages 6565-6580

  Serrano, Soraya ^a   Araujo, Aitziber ^b   Apellániz, Beatriz ^b   Bryson, Steve ^c,d   Carravilla, Pablo ^b   De La Arada, Igor ^b   Huarte, Nerea ^b   Rujas, Edurne ^b   Pai, Emil F ^c,d   Arrondo, José L R ^b   Domene, Carmen ^e,f   Jiménez, María Angeles ^a   Nieva, José L ^b  

^a INSTITUTO DE QUÍMICA FÍSICA ROCASOLANO   (Spain)

^b UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^c UNIVERSITY OF TORONTO   (Canada)

^d PRINCESS MARGARET HOSPITAL   (Canada)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODIES; EPITOPES; PEPTIDES;

ANTIBODY RECOGNITION; IMMUNOGENICITY; NEUTRALIZING ANTIBODIES; PEPTIDE EPITOPES; PEPTIDE VACCINES; VACCINE DEVELOPMENT;

VACCINES;

DODECYLPHOSPHORYLCHOLINE; FREUND ADJUVANT; HEXAFLUORO 2 PROPANOL; LIPOSOME; MEMBRANE PROXIMAL EXTERNAL REGION OF GP41; PEPTIDE VACCINE; UNCLASSIFIED DRUG;

ADSORPTION; AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOGENICITY; INFRARED SPECTROSCOPY; LIPID BILAYER; MEMBRANE; MEMBRANE BINDING; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ANALYSIS;

FOURIER TRANSFORM IR (FTIR); HIV-1; LIPOSOMES; NUCLEAR MAGNETIC RESONANCE; PEPTIDE CONFORMATION; VACCINE DEVELOPMENT;

AIDS VACCINES; AMINO ACID SEQUENCE; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; HIV ENVELOPE PROTEIN GP41; HUMANS; IMMUNODOMINANT EPITOPES; MICELLES; MOLECULAR SEQUENCE DATA; PHOSPHORYLCHOLINE; PROTEIN FOLDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; SPECTROPHOTOMETRY, INFRARED; VACCINES, SUBUNIT;

EID: 84896783592     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.527747     Document Type: Article

References (86)

1. Karlsson Hedestam, G. B., Fouchier, R. A., Phogat, S., Burton, D. R., Sodroski, J., and Wyatt, R. T. (2008) The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat. Rev. Microbiol. 6, 143-155
2. Merk, A., and Subramaniam, S. (2013) HIV-1 envelope glycoprotein structure. Curr. Opin. Struct. Biol. 23, 268-276
3. Melikyan, G. B. (2008) Common principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm. Retrovirology 5, 111
4. Wyatt, R., and Sodroski, J. (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884-1888
5. Blumenthal, R., Durell, S., and Viard, M. (2012) HIV entry and envelope glycoprotein-mediated fusion. J. Biol. Chem. 287, 40841-40849
6. Burton, D. R., Desrosiers, R. C., Doms, R. W., Koff, W. C., Kwong, P. D., Moore, J. P., Nabel, G. J., Sodroski, J., Wilson, I. A., and Wyatt, R. T. (2004) HIV vaccine design and the neutralizing antibody problem. Nat. Immunol. 5, 233-236
7. Stamatatos, L., Morris, L., Burton, D. R., and Mascola, J. R. (2009) Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat. Med. 15, 866-870
8. Mascola, J. R., and Montefiori, D. C. (2010) The role of antibodies in HIV vaccines. Annu. Rev. Immunol. 28, 413-444
9. Klein, F., Mouquet, H., Dosenovic, P., Scheid, J. F., Scharf, L., and Nussenzweig, M. C. (2013) Antibodies in HIV-1 vaccine development and therapy. Science 341, 1199-1204
10. Walker, L. M., and Burton, D. R. (2010) Rational antibody-based HIV-1 vaccine design: current approaches and future directions. Curr. Opin. Immunol. 22, 358-366
11. Kwong, P. D., and Mascola, J. R. (2012) Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37, 412-425
12. Gray, E. S., Madiga, M. C., Moore, P. L., Mlisana, K., Abdool Karim, S. S., Binley, J. M., Shaw, G. M., Mascola, J. R., and Morris, L. (2009) Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region. J. Virol. 83, 11265-11274
13. Zwick, M. B., Labrijn, A. F., Wang, M., Spenlehauer, C., Saphire, E. O., Binley, J. M., Moore, J. P., Stiegler, G., Katinger, H., Burton, D. R., and Parren, P. W. (2001) Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol. 75, 10892-10905
14. Ofek, G., Tang, M., Sambor, A., Katinger, H., Mascola, J. R., Wyatt, R., and Kwong, P. D. (2004) Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J. Virol. 78, 10724-10737
15. Cardoso, R. M., Brunel, F. M., Ferguson, S., Zwick, M., Burton, D. R., Dawson, P. E., and Wilson, I. A. (2007) Structural basis of enhanced binding of extended and helically constrained peptide epitopes of the broadly neutralizing HIV-1 antibody 4E10. J. Mol. Biol. 365, 1533-1544
16. Pejchal, R., Gach, J. S., Brunel, F. M., Cardoso, R. M., Stanfield, R. L., Dawson, P. E., Burton, D. R., Zwick, M. B., and Wilson, I. A. (2009) A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies. J. Virol. 83, 8451-8462
17. Zhu, Z., Qin, H. R., Chen, W., Zhao, Q., Shen, X., Schutte, R., Wang, Y., Ofek, G., Streaker, E., Prabakaran, P., Fouda, G. G., Liao, H. X., Owens, J., Louder, M., Yang, Y., Klaric, K. A., Moody, M. A., Mascola, J. R., Scott, J. K., Kwong, P. D., Montefiori, D., Haynes, B. F., Tomaras, G. D., and Dimitrov, D. S. (2011) Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies. J. Virol. 85, 11401-11408
18. Huang, J., Ofek, G., Laub, L., Louder, M. K., Doria-Rose, N. A., Longo, N. S., Imamichi, H., Bailer, R. T., Chakrabarti, B., Sharma, S. K., Alam, S. M., Wang, T., Yang, Y., Zhang, B., Migueles, S. A., Wyatt, R., Haynes, B. F., Kwong, P. D., Mascola, J. R., and Connors, M. (2012) Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491, 406-412
19. Montero, M., van Houten, N. E., Wang, X., and Scott, J. K. (2008) The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design. Microbiol. Mol. Biol. Rev. 72, 54-84
20. Montero, M., Gulzar, N., Klaric, K. A., Donald, J. E., Lepik, C., Wu, S., Tsai, S., Julien, J. P., Hessell, A. J., Wang, S., Lu, S., Burton, D. R., Pai, E. F., Degrado, W. F., and Scott, J. K. (2012) Neutralizing epitopes in the membrane-proximal external region of HIV-1 gp41 are influenced by the transmembrane domain and the plasma membrane. J. Virol. 86, 2930-2941
21. Muster, T., Steindl, F., Purtscher, M., Trkola, A., Klima, A., Himmler, G., Rüker, F., and Katinger, H. (1993) A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol. 67, 6642-6647
22. Muster, T., Guinea, R., Trkola, A., Purtscher, M., Klima, A., Steindl, F., Palese, P., and Katinger, H. (1994) Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS. J. Virol. 68, 4031-4034
23. Binley, J. M., Wrin, T., Korber, B., Zwick, M. B., Wang, M., Chappey, C., Stiegler, G., Kunert, R., Zolla-Pazner, S., Katinger, H., Petropoulos, C. J., and Burton, D. R. (2004) Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J. Virol. 78, 13232-13252
24. Conley, A. J., Kessler, J. A., 2nd, Boots, L. J., Tung, J. S., Arnold, B. A., Keller, P. M., Shaw, A. R., and Emini, E. A. (1994) Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody. Proc. Natl. Acad. Sci. U.S.A. 91, 3348-3352
25. Guenaga, J., and Wyatt, R. T. (2012) Structure-guided alterations of the gp41-directed HIV-1 broadly neutralizing antibody 2F5 reveal new properties regarding its neutralizing function. PLoS Pathog. 8, e1002806
26. Purtscher, M., Trkola, A., Gruber, G., Buchacher, A., Predl, R., Steindl, F., Tauer, C., Berger, R., Barrett, N., and Jungbauer, A. (1994) A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses 10, 1651-1658
27. Coëffier, E., Clément, J. M., Cussac, V., Khodaei-Boorane, N., Jehanno, M., Rojas, M., Dridi, A., Latour, M., El Habib, R., Barré-Sinoussi, F., Hofnung, M., and Leclerc, C. (2000) Antigenicity and immunogenicity of the HIV-1 gp41 epitope ELDKWA inserted into permissive sites of the MalE protein. Vaccine 19, 684-693
28. McGaughey, G. B., Citron, M., Danzeisen, R. C., Freidinger, R. M., Garsky, V. M., Hurni, W. M., Joyce, J. G., Liang, X., Miller, M., Shiver, J., and Bogusky, M. J. (2003) HIV-1 vaccine development: constrained peptide immunogens show improved binding to the anti-HIV-1 gp41 MAb. Biochemistry 42, 3214-3223
29. Dennison, S. M., Sutherland, L. L., Jaeger, F. H., Anasti, K. M., Parks, R., Stewart, S., Bowman, C., Xia, S. M., Zhang, R., Shen, X., Scearce, R. M., Ofek, G., Yang, Y., Kwong, P. D., Santra, S., Liao, H. X., Tomaras, G., Letvin, N. L., Chen, B., Alam, S. M., and Haynes, B. F. (2011) Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41. PLoS One 6, e27824
30. Guenaga, J., Dosenovic, P., Ofek, G., Baker, D., Schief, W. R., Kwong, P. D., Karlsson Hedestam, G. B., and Wyatt, R. T. (2011) Heterologous epitopescaffold prime:boosting immuno-focuses B cell responses to the HIV-1 gp41 2F5 neutralization determinant. PLoS One 6, e16074
31. Matyas, G. R., Wieczorek, L., Beck, Z., Ochsenbauer-Jambor, C., Kappes, J. C., Michael, N. L., Polonis, V. R., and Alving, C. R. (2009) Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes. AIDS 23, 2069-2077
32. Huarte, N., Araujo, A., Arranz, R., Lorizate, M., Quendler, H., Kunert, R., Valpuesta, J. M., and Nieva, J. L. (2012) Recognition of membrane-bound fusion-peptide/MPER complexes by the HIV-1 neutralizing 2F5 antibody: implications for anti-2F5 immunogenicity. PLoS One 7, e52740
33. Joyce, J. G., Hurni, W. M., Bogusky, M. J., Garsky, V. M., Liang, X., Citron, M. P., Danzeisen, R. C., Miller, M. D., Shiver, J. W., and Keller, P. M. (2002) Enhancement ofhelicity in the HIV-1 inhibitory peptide DP178 leads to an increased affinity for human monoclonal antibody 2F5 but does not elicit neutralizing responses in vitro. Implications for vaccine design. J. Biol. Chem. 277, 45811-45820
34. Parker, C. E., Deterding, L. J., Hager-Braun, C., Binley, J. M., Schülke, N., Katinger, H., Moore, J. P., and Tomer, K. B. (2001) Fine definition of the epitope on the gp41 glycoprotein of human immunodeficiency virus type 1 for the neutralizing monoclonal antibody 2F5. J. Virol. 75, 10906-10911
35. Barbato, G., Bianchi, E., Ingallinella, P., Hurni, W. H., Miller, M. D., Ciliberto, G., Cortese, R., Bazzo, R., Shiver, J. W., and Pessi, A. (2003) Structural analysis of the epitope of the anti-HIV antibody 2F5 sheds light into its mechanism of neutralization and HIV fusion. J. Mol. Biol. 330, 1101-1115
36. Julien, J. P., Bryson, S., Nieva, J. L., and Pai, E. F. (2008) Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anionbinding site. J. Mol. Biol. 384, 377-392
37. Zwick, M. B., Komori, H. K., Stanfield, R. L., Church, S., Wang, M., Parren, P. W., Kunert, R., Katinger, H., Wilson, I. A., and Burton, D. R. (2004) The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5. J. Virol. 78, 3155-3161
38. Julien, J. P., Huarte, N., Maeso, R., Taneva, S. G., Cunningham, A., Nieva, J. L., and Pai, E. F. (2010) Ablation of the complementarity-determining region H3 apex of the anti-HIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding. J. Virol. 84, 4136-4147
39. Sánchez-Martínez, S., Lorizate, M., Katinger, H., Kunert, R., and Nieva, J. L. (2006) Membrane association and epitope recognition by HIV-1 neutralizing anti-gp41 2F5 and 4E10 antibodies. AIDS Res. Hum. Retroviruses 22, 998-1006
40. Kim, M., Sun, Z. Y., Rand, K. D., Shi, X., Song, L., Cheng, Y., Fahmy, A. F., Majumdar, S., Ofek, G., Yang, Y., Kwong, P. D., Wang, J. H., Engen, J. R., Wagner, G., and Reinherz, E. L. (2011) Antibody mechanics on a membrane-bound HIV segment essential for GP41-targeted viral neutralization. Nat. Struct. Mol. Biol. 18, 1235-1243
41. Alam, S. M., Morelli, M., Dennison, S. M., Liao, H. X., Zhang, R., Xia, S. M., Rits-Volloch, S., Sun, L., Harrison, S. C., Haynes, B. F., and Chen, B. (2009) Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc. Natl. Acad. Sci. U.S.A. 106, 20234-20239
42. Mirassou, Y., Santiveri, C. M., Pérez de Vega, M. J., González-Muñiz, R., and Jiménez, M. A. (2009) Disulfide bonds versus TrpTrp pairs in irregular hairpins: NMR structure of vammin loop 3-derived peptides as a case study. ChemBioChem 10, 902-910
43. Cornilescu, G., Delaglio, F., and Bax, A. (1999) Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J. Biomol. NMR 13, 289-302
44. Güntert, P., Mumenthaler, C., and Wüthrich, K. (1997) Torsion angle dynamics for NMR structure calculation with the new program DYANA. J. Mol. Biol. 273, 283-298
45. Güntert, P. (2004) Automated NMR structure calculation with CYANA. Methods Mol. Biol. 278, 353-378
46. Laskowski, R. A., Rullmannn, J. A., MacArthur, M. W., Kaptein, R., and Thornton, J. M. (1996) AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J. Biomol. NMR 8, 477-486
47. Koradi, R., Billeter, M., and Wüthrich, K. (1996) MOLMOL: a program for display and analysis of macromolecular structures. J. Mol. Graph. 14, 51-55
48. Guex, N., and Peitsch, M. C. (1997) SWISS-MODEL and the Swiss-Pdb-Viewer: an environment for comparative protein modeling. Electrophoresis 18, 2714-2723
49. Yethon, J. A., Epand, R. F., Leber, B., Epand, R. M., and Andrews, D. W. (2003) Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis. J. Biol. Chem. 278, 48935-48941
50. Arrondo, J. L., and Goñi, F. M. (1999) Structure and dynamics of membrane proteins as studied by infrared spectroscopy. Prog. Biophys. Mol. Biol. 72, 367-405
51. Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., and Schulten, K. (2005) Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781-1802
52. MacKerell, A. D., Bashford, D., Bellott, Dunbrack, R. L., Evanseck, J. D., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F. T. K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D. T., Prodhom, B., Reiher, W. E., Roux, B., Schlenkrich, M., Smith, J. C., Stote, R., Straub, J., Watanabe, M., Wiórkiewicz-Kuczera, J., Yin, D., and Karplus, M. (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102, 3586-3616
53. Klauda, J. B., Venable, R. M., Freites, J. A., O'Connor, J. W., Tobias, D. J., Mondragon-Ramirez, C., Vorobyov, I., MacKerell, A. D., Jr., and Pastor, R. W. (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Phys. Chem. B. 114, 7830-7843
54. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., and Klein, M. L. (1983) Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926-935
55. Cournia, Z., Smith, J. C., and Ullmann, G. M. (2005) A molecular mechanics force field for biologically important sterols. J. Comput. Chem. 26, 1383-1399
56. Martyna, G. J., Tobias, D. J., and Klein, M. L. (1994) Constant pressure molecular dynamics algorithms. J. Chem. Phys. 101, 4177-4189
57. Feller, S. E., Zhang, Y., Pastor, R. W., and Brooks, B. R. (1995) Constant pressure molecular dynamics simulation: the Langevin piston method. J. Chem. Phys. 103, 4613-4621
58. Essmann, U., Perera, L., and Berkowitz, M. (1995) A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577-8593
59. Miyamoto, S., and Kollman, P. (1992) Settle: an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comput. Chem. 13, 952-962
60. Dreesman, G. R., Sanchez, Y., Ionescu-Matiu, I., Sparrow, J. T., Six, H. R., Peterson, D. L., Hollinger, F. B., and Melnick, J. L. (1982) Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptides. Nature 295, 158-160
61. Maeso, R., Huarte, N., Julien, J. P., Kunert, R., Pai, E. F., and Nieva, J. L. (2011) Interaction of anti-HIV type 1 antibody 2F5 with phospholipid bilayers and its relevance for the mechanism of virus neutralization. AIDS Res. Hum. Retroviruses 27, 863-876
62. Alving, C. R., Rao, M., Steers, N. J., Matyas, G. R., and Mayorov, A. V. (2012) Liposomes containing lipid A: an effective, safe, generic adjuvant system for synthetic vaccines. Expert Rev. Vaccines 11, 733-744
63. Menendez, A., Chow, K. C., Pan, O. C., and Scott, J. K. (2004) Human immunodeficiency virus type 1-neutralizing monoclonal antibody 2F5 is multispecific for sequences flanking the DKW core epitope. J. Mol. Biol. 338, 311-327
64. Wuthrich, K. (1986) NMR of Proteins and Nucleic Acids. John Wiley & Sons, Inc., New York
65. Wüthrich, K., Billeter, M., and Braun, W. (1984) Polypeptide secondary structure determination by nuclear magnetic resonance observation of short proton-proton distances. J. Mol. Biol. 180, 715-740
66. Wishart, D. S., Bigam, C. G., Holm, A., Hodges, R. S., and Sykes, B. D. (1995) 1H, 13C, and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. J. Biomol. NMR 5, 67-81
67. Reisdorf, W. C., Jr., and Krimm, S. (1996) Infrared amide I band of the coiled coil. Biochemistry 35, 1383-1386
68. Walsh, S. T., Cheng, R. P., Wright, W. W., Alonso, D. O., Daggett, V., Vanderkooi, J. M., and DeGrado, W. F. (2003) The hydration of amides in helices; a comprehensive picture from molecular dynamics, IR, and NMR. Protein Sci. 12, 520-531
69. Vu, D. M., Myers, J. K., Oas, T. G., and Dyer, R. B. (2004) Probing the folding and unfolding dynamics of secondary and tertiary structures in a three-helix bundle protein. Biochemistry 43, 3582-3589
70. Coffman, R. L., Sher, A., and Seder, R. A. (2010) Vaccine adjuvants: putting innate immunity to work. Immunity 33, 492-503
71. Mukherjee, S., Chowdhury, P., DeGrado, W. F., and Gai, F. (2007) Sitespecific hydration status of an amphipathic peptide in AOT reverse micelles. Langmuir 23, 11174-11179
72. Lorizate, M., Huarte, N., Sáez-Cirión, A., and Nieva, J. L. (2008) Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission. Biochim. Biophys. Acta 1778, 1624-1639
73. Sun, Z. Y., Oh, K. J., Kim, M., Yu, J., Brusic, V., Song, L., Qiao, Z., Wang, J. H., Wagner, G., and Reinherz, E. L. (2008) HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity 28, 52-63
74. Suárez, T., Gallaher, W. R., Agirre, A., Goñi, F. M., and Nieva, J. L. (2000) Membrane interface-interacting sequences within the ectodomain of the human immunodeficiency virus type 1 envelope glycoprotein: putative role during viral fusion. J. Virol. 74, 8038-8047
75. Biron, Z., Khare, S., Samson, A. O., Hayek, Y., Naider, F., and Anglister, J. (2002) A monomeric 310-helix is formed in water by a 13-residue peptide representing the neutralizing determinant of HIV-1 on gp41. Biochemistry 41, 12687-12696
76. Schibli, D. J., Montelaro, R. C., and Vogel, H. J. (2001) The membraneproximal tryptophan-rich region of the HIV glycoprotein, gp41, forms a well defined helix in dodecylphosphocholine micelles. Biochemistry 40, 9570-9578
77. Coutant, J., Yu, H., Clément, M. J., Alfsen, A., Toma, F., Curmi, P. A., and Bomsel, M. (2008) Both lipid environment and pH are critical for determining physiological solution structure of 3-D-conserved epitopes of the HIV-1 gp41-MPER peptide P1. FASEB J. 22, 4338-4351
78. Bryson, S., Julien, J. P., Hynes, R. C., and Pai, E. F. (2009) Crystallographic definition of the epitope promiscuity of the broadly neutralizing antihuman immunodeficiency virus type 1 antibody 2F5: vaccine design implications. J. Virol. 83, 11862-11875
79. Depetris, R. S., Julien, J. P., Khayat, R., Lee, J. H., Pejchal, R., Katpally, U., Cocco, N., Kachare, M., Massi, E., David, K. B., Cupo, A., Marozsan, A. J., Olson, W. C., Ward, A. B., Wilson, I. A., Sanders, R. W., and Moore, J. P. (2012) Partial enzymatic deglycosylation preserves the structure of cleaved recombinant HIV-1 envelope glycoprotein trimers. J. Biol. Chem. 287, 24239-24254
80. Julien, J. P., Cupo, A., Sok, D., Stanfield, R. L., Lyumkis, D., Deller, M. C., Klasse, P. J., Burton, D. R., Sanders, R. W., Moore, J. P., Ward, A. B., and Wilson, I. A. (2013) Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477-1483
81. Jones, L. S., Peek, L. J., Power, J., Markham, A., Yazzie, B., and Middaugh, C. R. (2005) Effects of adsorption to aluminum salt adjuvants on the structure and stability of model protein antigens. J. Biol. Chem. 280, 13406-13414
82. Dokter, A. M., Woutersen, S., and Bakker, H. J. (2006) Inhomogeneous dynamics in confined water nanodroplets. Proc. Natl. Acad. Sci. U.S.A. 103, 15355-15358
83. Zwick, M. B. (2005) The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring. Aids 19, 1725-1737
84. Haris, P. I., Ramesh, B., Brazier, S., and Chapman, D. (1994) The conformational analysis of a synthetic S4 peptide corresponding to a voltagegated potassium ion channel protein. FEBS Lett. 349, 371-374
85. Polonis, V. R., Brown, B. K., Rosa Borges, A., Zolla-Pazner, S., Dimitrov, D. S., Zhang, M. Y., Barnett, S. W., Ruprecht, R. M., Scarlatti, G., Fenyö, E. M., Montefiori, D. C., McCutchan, F. E., and Michael, N. L. (2008) Recent advances in the characterization of HIV-1 neutralization assays for standardized evaluation of the antibody response to infection and vaccination. Virology 375, 315-320
86. Gulzar, N., Klaric, K., Parfyonov, M., Montero, M., Wang, S., Huarte, N., Appellaniz, B., Nieva, J., Lu, S., and Scott, J. (2013) Study 1: Optimizing vaccines that target the 2F5 epitope of the membrane proximal external region of HIV-1 gp41. AIDS Res. Hum. Retroviruses 29, 13-63