A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic β-Hairpin Structure

Immunity

Volumn 46, Issue 4, 2017, Pages 690-702

  Lee, Jeong Hyun ^a   Andrabi, Raiees ^a   Su, Ching Yao ^a   Yasmeen, Anila ^b   Julien, Jean Philippe ^a,c   Kong, Leopold ^a   Wu, Nicholas C ^a   McBride, Ryan ^a   Sok, Devin ^a   Pauthner, Matthias ^a   Cottrell, Christopher A ^a   Nieusma, Travis ^a   Blattner, Claudia ^a   Paulson, James C ^a   Klasse, Per Johan ^b   Wilson, Ian A ^a   Burton, Dennis R ^a,d   Ward, Andrew B ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

^d MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

broadly neutralizing antibody; cryo electron microscopy; envelope glycoprotein; HIV; PGT145; trimer apex

Indexed keywords

GLYCAN DERIVATIVE; HEAVY CHAIN COMPLEMENTARITY DETERMINING REGION 3; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; ANION; EPITOPE; POLYSACCHARIDE; PROTEIN BINDING;

ALLOSTERISM; ANTIBODY STRUCTURE; ARTICLE; BINDING SITE; CONFORMATIONAL TRANSITION; CRYOELECTRON MICROSCOPY; HUMAN IMMUNODEFICIENCY VIRUS; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN GLYCOSYLATION; RECEPTOR BINDING; SOMATIC HYPERMUTATION; STOICHIOMETRY; VIRUS ENTRY; AMINO ACID SEQUENCE; CHEMISTRY; HEK293 CELL LINE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; METABOLISM; MOLECULAR MODEL; PROTEIN DOMAIN; PROTEIN MULTIMERIZATION; PROTEIN SECONDARY STRUCTURE; SEQUENCE HOMOLOGY; SURFACE PLASMON RESONANCE; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIONS; ANTIBODIES, NEUTRALIZING; CRYOELECTRON MICROSCOPY; CRYSTALLOGRAPHY, X-RAY; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITOPES; HEK293 CELLS; HIV ANTIBODIES; HIV-1; HUMANS; MODELS, MOLECULAR; POLYSACCHARIDES; PROTEIN BINDING; PROTEIN DOMAINS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, SECONDARY; SEQUENCE HOMOLOGY, AMINO ACID; SURFACE PLASMON RESONANCE;

EID: 85019040760     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2017.03.017     Document Type: Article

References (51)

1. Adams, P.D., Afonine, P.V., Bunkoczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.W., Kapral, G.J., Grosse-Kunstleve, R.W., et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr., Sect: D Biol. Crystallogr. 66 (2010), 213–221.
2. Andrabi, R., Voss, J.E., Liang, C.H., Briney, B., McCoy, L.E., Wu, C.Y., Wong, C.H., Poignard, P., Burton, D.R., Identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design. Immunity 43 (2015), 959–973.
3. Barad, B.A., Echols, N., Wang, R.Y., Cheng, Y., DiMaio, F., Adams, P.D., Fraser, J.S., EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. Nat. Methods 12 (2015), 943–946.
4. Blattner, C., Lee, J.H., Sliepen, K., Derking, R., Falkowska, E., de la Peña, A.T., Cupo, A., Julien, J.P., van Gils, M., Lee, P.S., et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity 40 (2014), 669–680.
5. Burton, D.R., Hangartner, L., Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu. Rev. Immunol. 34 (2016), 635–659.
6. Chen, V.B., Arendall, W.B. 3rd, Headd, J.J., Keedy, D.A., Immormino, R.M., Kapral, G.J., Murray, L.W., Richardson, J.S., Richardson, D.C., MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. Sect: D. Biol. Crystallogr. 66 (2010), 12–21.
7. Cheng, C., Pancera, M., Bossert, A., Schmidt, S.D., Chen, R.E., Chen, X., Druz, A., Narpala, S., Doria-Rose, N.A., McDermott, A.B., et al. Immunogenicity of a prefusion HIV-1 envelope trimer in complex with a quaternary-structure-specific antibody. J. Virol. 90 (2015), 2740–2755.
8. Curlin, M.E., Zioni, R., Hawes, S.E., Liu, Y., Deng, W., Gottlieb, G.S., Zhu, T., Mullins, J.I., HIV-1 envelope subregion length variation during disease progression. PLoS Pathog., 6, 2010, e1001228.
9. de Taeye, S.W., Ozorowski, G., Torrents de la Peña, A., Guttman, M., Julien, J.P., van den Kerkhof, T.L., Burger, J.A., Pritchard, L.K., Pugach, P., Yasmeen, A., et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell 163 (2015), 1702–1715.
10. Derking, R., Ozorowski, G., Sliepen, K., Yasmeen, A., Cupo, A., Torres, J.L., Julien, J.P., Lee, J.H., van Montfort, T., de Taeye, S.W., et al. Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLoS Pathog., 11, 2015, e1004767.
11. Derrick, J.P., Wigley, D.B., The third IgG-binding domain from streptococcal protein G. An analysis by X-ray crystallography of the structure alone and in a complex with Fab. J. Mol. Biol. 243 (1994), 906–918.
12. DiMaio, F., Tyka, M.D., Baker, M.L., Chiu, W., Baker, D., Refinement of protein structures into low-resolution density maps using rosetta. J. Mol. Biol. 392 (2009), 181–190.
13. Doria-Rose, N.A., Georgiev, I., O'Dell, S., Chuang, G.Y., Staupe, R.P., McLellan, J.S., Gorman, J., Pancera, M., Bonsignori, M., Haynes, B.F., et al. A short segment of the HIV-1 gp120 V1/V2 region is a major determinant of resistance to V1/V2 neutralizing antibodies. J. Virol. 86 (2012), 8319–8323.
14. Doria-Rose, N.A., Schramm, C.A., Gorman, J., Moore, P.L., Bhiman, J.N., DeKosky, B.J., Ernandes, M.J., Georgiev, I.S., Kim, H.J., Pancera, M., et al., NISC Comparative Sequencing Program. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509 (2014), 55–62.
15. Doria-Rose, N.A., Bhiman, J.N., Roark, R.S., Schramm, C.A., Gorman, J., Chuang, G.Y., Pancera, M., Cale, E.M., Ernandes, M.J., Louder, M.K., et al. New member of the V1V2-directed CAP256-VRC26 lineage that shows increased breadth and exceptional potency. J. Virol. 90 (2015), 76–91.
16. Edgar, R.C., MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32 (2004), 1792–1797.
17. Ekiert, D.C., Kashyap, A.K., Steel, J., Rubrum, A., Bhabha, G., Khayat, R., Lee, J.H., Dillon, M.A., O'Neil, R.E., Faynboym, A.M., et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489 (2012), 526–532.
18. Emsley, P., Lohkamp, B., Scott, W.G., Cowtan, K., Features and development of Coot. Acta Crystallogr., Sect: D Biol. Crystallogr. 66 (2010), 486–501.
19. Gorman, J., Soto, C., Yang, M.M., Davenport, T.M., Guttman, M., Bailer, R.T., Chambers, M., Chuang, G.Y., DeKosky, B.J., Doria-Rose, N.A., et al., NISC Comparative Sequencing Program. Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat. Struct. Mol. Biol. 23 (2016), 81–90.
20. Henikoff, S., Henikoff, J.G., Amino acid substitution matrices from protein blocks. Proc. Natl. Acad. Sci. USA 89 (1992), 10915–10919.
21. 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., et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342 (2013), 1477–1483.
22. Julien, J.P., Lee, J.H., Cupo, A., Murin, C.D., Derking, R., Hoffenberg, S., Caulfield, M.J., King, C.R., Marozsan, A.J., Klasse, P.J., et al. Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc. Natl. Acad. Sci. USA 110 (2013), 4351–4356.
23. Klein, F., Diskin, R., Scheid, J.F., Gaebler, C., Mouquet, H., Georgiev, I.S., Pancera, M., Zhou, T., Incesu, R.B., Fu, B.Z., et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 153 (2013), 126–138.
24. Kwon, Y.D., Pancera, M., Acharya, P., Georgiev, I.S., Crooks, E.T., Gorman, J., Joyce, M.G., Guttman, M., Ma, X., Narpala, S., et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat. Struct. Mol. Biol. 22 (2015), 522–531.
25. Lee, J.H., de Val, N., Lyumkis, D., Ward, A.B., Model Building and Refinement of a Natively Glycosylated HIV-1 Env protein by high-resolution cryoelectron microscopy. Structure 23 (2015), 1943–1951.
26. Liu, J., Bartesaghi, A., Borgnia, M.J., Sapiro, G., Subramaniam, S., Molecular architecture of native HIV-1 gp120 trimers. Nature 455 (2008), 109–113.
27. McCoy, A.J., Grosse-Kunstleve, R.W., Adams, P.D., Winn, M.D., Storoni, L.C., Read, R.J., Phaser crystallographic software. J. Appl. Cryst. 40 (2007), 658–674.
28. McLellan, J.S., Pancera, M., Carrico, C., Gorman, J., Julien, J.P., Khayat, R., Louder, R., Pejchal, R., Sastry, M., Dai, K., et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 480 (2011), 336–343.
29. Ogura, T., Iwasaki, K., Sato, C., Topology representing network enables highly accurate classification of protein images taken by cryo electron-microscope without masking. J. Struct. Biol. 143 (2003), 185–200.
30. Otwinowski, Z., Minor, W., Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276A (1997), 307–326.
31. Pancera, M., Shahzad-Ul-Hussan, S., Doria-Rose, N.A., McLellan, J.S., Bailer, R.T., Dai, K., Loesgen, S., Louder, M.K., Staupe, R.P., Yang, Y., et al. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16. Nat. Struct. Mol. Biol. 20 (2013), 804–813.
32. Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Blondel, M., Prettenhofer, P., Weiss, R., Dubourg, V., et al. Scikit-learn: Machine Learning in Python. J. Mach. Learn. Res. 12 (2011), 2825–2830.
33. Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25 (2004), 1605–1612.
34. Pugach, P., Ozorowski, G., Cupo, A., Ringe, R., Yasmeen, A., de Val, N., Derking, R., Kim, H.J., Korzun, J., Golabek, M., et al. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J. Virol. 89 (2015), 3380–3395.
35. Rizzuto, C.D., Wyatt, R., Hernández-Ramos, N., Sun, Y., Kwong, P.D., Hendrickson, W.A., Sodroski, J., A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280 (1998), 1949–1953.
36. Rusert, P., Kouyos, R.D., Kadelka, C., Ebner, H., Schanz, M., Huber, M., Braun, D.L., Hozé, N., Scherrer, A., Magnus, C., et al., Swiss HIV Cohort Study. Determinants of HIV-1 broadly neutralizing antibody induction. Nat. Med. 22 (2016), 1260–1267.
37. Sagar, M., Wu, X., Lee, S., Overbaugh, J., Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J. Virol. 80 (2006), 9586–9598.
38. Sanders, R.W., Derking, R., Cupo, A., Julien, J.P., Yasmeen, A., de Val, N., Kim, H.J., Blattner, C., de la Peña, A.T., Korzun, J., et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog., 9, 2013, e1003618.
39. Scharf, L., West, A.P., Sievers, S.A., Chen, C., Jiang, S., Gao, H., Gray, M.D., McGuire, A.T., Scheid, J.F., Nussenzweig, M.C., et al. Structural basis for germline antibody recognition of HIV-1 immunogens. eLife, 5, 2016, 5.
40. Scheres, S.H., RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180 (2012), 519–530.
41. Sok, D., van Gils, M.J., Pauthner, M., Julien, J.P., Saye-Francisco, K.L., Hsueh, J., Briney, B., Lee, J.H., Le, K.M., Lee, P.S., et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc. Natl. Acad. Sci. USA 111 (2014), 17624–17629.
42. Steichen, J.M., Kulp, D.W., Tokatlian, T., Escolano, A., Dosenovic, P., Stanfield, R.L., McCoy, L.E., Ozorowski, G., Hu, X., Kalyuzhniy, O., et al. HIV vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies. Immunity 45 (2016), 483–496.
43. Suloway, C., Pulokas, J., Fellmann, D., Cheng, A., Guerra, F., Quispe, J., Stagg, S., Potter, C.S., Carragher, B., Automated molecular microscopy: the new Leginon system. J. Struct. Biol. 151 (2005), 41–60.
44. Walker, L.M., Phogat, S.K., Chan-Hui, P.Y., Wagner, D., Phung, P., Goss, J.L., Wrin, T., Simek, M.D., Fling, S., Mitcham, J.L., et al., Protocol G Principal Investigators. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326 (2009), 285–289.
45. Walker, L.M., Huber, M., Doores, K.J., Falkowska, E., Pejchal, R., Julien, J.P., Wang, S.K., Ramos, A., Chan-Hui, P.Y., Moyle, M., et al., Protocol G Principal Investigators. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477 (2011), 466–470.
46. Wang, S.K., Liang, P.H., Astronomo, R.D., Hsu, T.L., Hsieh, S.L., Burton, D.R., Wong, C.H., Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc. Natl. Acad. Sci. USA 105 (2008), 3690–3695.
47. Wang, F., Ekiert, D.C., Ahmad, I., Yu, W., Zhang, Y., Bazirgan, O., Torkamani, A., Raudsepp, T., Mwangi, W., Criscitiello, M.F., et al. Reshaping antibody diversity. Cell 153 (2013), 1379–1393.
48. Webb, B., Sali, A., Comparative Protein Structure Modeling Using MODELLER. Curr. Protoc. Bioinformatics, 54, 2016 5 6 1-5 6 37.
49. Wu, L., Gerard, N.P., Wyatt, R., Choe, H., Parolin, C., Ruffing, N., Borsetti, A., Cardoso, A.A., Desjardin, E., Newman, W., et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 384 (1996), 179–183.
50. Yacoob, C., Pancera, M., Vigdorovich, V., Oliver, B.G., Glenn, J.A., Feng, J., Sather, D.N., McGuire, A.T., Stamatatos, L., Differences in allelic frequency and CDRH3 region limit the engagement of HIV env immunogens by putative VRC01 neutralizing antibody precursors. Cell Rep. 17 (2016), 1560–1570.
51. Yasmeen, A., Ringe, R., Derking, R., Cupo, A., Julien, J.P., Burton, D.R., Ward, A.B., Wilson, I.A., Sanders, R.W., Moore, J.P., Klasse, P.J., Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology, 11, 2014, 41.