Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site

Nature Structural and Molecular Biology

Volumn 23, Issue 10, 2016, Pages 906-915

  Gristick, Harry B ^a   Von Boehmer, Lotta ^b   West, Anthony P ^a   Schamber, Michael ^a   Gazumyan, Anna ^b   Golijanin, Jovana ^b   Seaman, Michael S ^c   Fätkenheuer, Gerd ^d,e   Klein, Florian ^d,e,f   Nussenzweig, Michel C ^b   Bjorkman, Pamela J ^a  

^a California Institute of Technology   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

^c BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^d UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^e UNIVERSITY OF BONN   (Germany)

^f UNIVERSITY OF COLOGNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CD4 ANTIBODY; GLYCAN; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; MANNOSE; NEUTRALIZING ANTIBODY; VIRUS ENVELOPE PROTEIN; CD4 ANTIGEN; EPITOPE; POLYSACCHARIDE;

ALPHA HELIX; ANTIBODY COMBINING SITE; ARTICLE; CARBOXY TERMINAL SEQUENCE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CRYSTALLIZATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HYDROGEN BOND; MOLECULAR RECOGNITION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN GLYCOSYLATION; PROTEIN STRUCTURE; CHEMISTRY; GLYCOSYLATION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; MOLECULAR MODEL; PROTEIN MULTIMERIZATION; VIROLOGY; X RAY CRYSTALLOGRAPHY;

ANTIBODIES, NEUTRALIZING; ANTIGENS, CD4; CRYSTALLOGRAPHY, X-RAY; EPITOPES; GLYCOSYLATION; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; MANNOSE; MODELS, MOLECULAR; POLYSACCHARIDES; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION;

EID: 84987652813     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.3291     Document Type: Article

References (62)

1. Lasky, L.A. et al. Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein. Science 233, 209-212 (1986).
2. Kwong, P.D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648-659 (1998).
3. Julien, J.P. et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477-1483 (2013).
4. Pancera, M. et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514, 455-461 (2014).
5. Scharf, L. et al. Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 Env. Cell 162, 1379-1390 (2015).
6. Garces, F. et al. Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding glycans. Immunity 43, 1053-1063 (2015).
7. 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, 1943-1951 (2015).
8. Lee, J.H., Ozorowski, G., Ward, A.B. Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 351, 1043-1048 (2016).
9. Stewart-Jones, G.B.E. et al. Trimeric HIV-1-Env structures define glycan shields from clades A, B, and G. Cell 165, 813-826 (2016).
10. Doores, K.J. The HIV glycan shield as a target for broadly neutralizing antibodies. FEBS J. 282, 4679-4691 (2015).
11. Behrens, A.J. et al. Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein. Cell Rep. 14, 2695-2706 (2016).
12. Binley, J.M. et al. Role of complex carbohydrates in human immunodeficiency virus type 1 infection and resistance to antibody neutralization. J. Virol. 84, 5637-5655 (2010).
13. Diskin, R. et al. Restricting HIV-1 pathways for escape using rationally designed anti-HIV-1 antibodies. J. Exp. Med. 210, 1235-1249 (2013).
14. Diskin, R. et al. Increasing the potency and breadth of an HIV antibody by using structure-based rational design. Science 334, 1289-1293 (2011).
15. Kwon, Y.D. et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat. Struct. Mol. Biol. 22, 522-531 (2015).
16. Kong, L. et al. Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer. Acta Crystallogr. D Biol. Crystallogr. 71, 2099-2108 (2015).
17. Scharf, L. et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep. 7, 785-795 (2014).
18. Zhou, T. et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329, 811-817 (2010).
19. Zhou, T. et al. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell 161, 1280-1292 (2015).
20. Zhou, T. et al. Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity 39, 245-258 (2013).
21. Jardine, J. et al. Rational HIV immunogen design to target specific germline B cell receptors. Science 340, 711-716 (2013).
22. Jardine, J.G. et al. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science 349, 156-161 (2015).
23. McGuire, A.T. et al. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science 346, 1380-1383 (2014).
24. McGuire, A.T. et al. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat. Commun. 7, 10618 (2016).
25. Jardine, J.G. et al. HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 351, 1458-1463 (2016).
26. McGuire, A.T. et al. Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies. J. Exp. Med. 210, 655-663 (2013).
27. Dosenovic, P. et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell 161, 1505-1515 (2015).
28. Wu, X. et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329, 856-861 (2010).
29. West, A.P. Jr., Diskin, R., Nussenzweig, M.C., Bjorkman, P.J. Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120. Proc. Natl. Acad. Sci. USA 109, E2083-E2090 (2012).
30. Mouquet, H. et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc. Natl. Acad. Sci. USA 109, E3268-E3277 (2012).
31. Scheid, J.F. et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636-640 (2009).
32. Bonsignori, M. et al. Maturation pathway from germline to broad HIV-1 neutralizer of a CD4-mimic antibody. Cell 165, 449-463 (2016).
33. Scheid, J.F. et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333, 1633-1637 (2011).
34. Sanders, R.W. 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, e1003618 (2013).
35. Adams, P.D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
36. Go, E.P. et al. Characterization of glycosylation profiles of HIV-1 transmitted/founder envelopes by mass spectrometry. J. Virol. 85, 8270-8284 (2011).
37. Agirre, J. et al. Privateer: software for the conformational validation of carbohydrate structures. Nat. Struct. Mol. Biol. 22, 833-834 (2015).
38. Kong, L. et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat. Struct. Mol. Biol. 20, 796-803 (2013).
39. Pejchal, R. et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334, 1097-1103 (2011).
40. Scharf, L. et al. Structural basis for germline antibody recognition of HIV-1 immunogens. eLife 5, e13783 (2016).
41. Adolf-Bryfogle, J., Xu, Q., North, B., Lehmann, A., Dunbrack, R.L. Jr. PyIgClassify: a database of antibody CDR structural classifications. Nucleic Acids Res. 43, D432-D438 (2015).
42. North, B., Lehmann, A., Dunbrack, R.L. Jr. A new clustering of antibody CDR loop conformations. J. Mol. Biol. 406, 228-256 (2011).
43. Lee, J.H. et al. Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike. Nat. Commun. 6, 8167 (2015).
44. McLellan, J.S. et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 480, 336-343 (2011).
45. Pancera, M. et al. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16. Nat. Struct. Mol. Biol. 20, 804-813 (2013).
46. Crooks, E.T. et al. Vaccine-elicited tier 2 HIV-1 neutralizing antibodies bind to quaternary epitopes involving glycan-deficient patches proximal to the CD4 binding site. PLoS Pathog. 11, e1004932 (2015).
47. Murugan, R., Imkeller, K., Busse, C.E., Wardemann, H. Direct high-throughput amplification and sequencing of immunoglobulin genes from single human B cells. Eur. J. Immunol. 45, 2698-2700 (2015).
48. Tiller, T. et al. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329, 112-124 (2008).
49. von Boehmer, L. et al. Antigen-specific antibodies from mouse memory B cells. Nat. Protoc. (in the press) (2016).
50. Montefiori, D.C. Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays. Curr. Protoc. Immunol. 64, 12.11 (2005).
51. Sheskin, D. Handbook of Parametric and Nonparametric Statistical Procedures 3rd edn. (Chapman & Hall/CRC, 2004).
52. Galimidi, R.P. et al. Intra-spike crosslinking overcomes antibody evasion by HIV-1. Cell 160, 433-446 (2015).
53. Kabsch, W. Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr. D Biol. Crystallogr. 66, 133-144 (2010).
54. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760-763 (1994).
55. Jaroszewski, L., Li, Z., Cai, X.H., Weber, C., Godzik, A. FFAS server: novel features and applications. Nucleic Acids Res. 39, W38-W44 (2011).
56. Emsley, P., Lohkamp, B., Scott, W.G., Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
57. Krissinel, E., Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007).
58. Pettersen, E.F. et al. UCSF Chimera: a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612 (2004).
59. Krissinel, E., Henrick, K. Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr. D Biol. Crystallogr. 60, 2256-2268 (2004).
60. Kleywegt, G.J. Use of non-crystallographic symmetry in protein structure refinement. Acta Crystallogr. D Biol. Crystallogr. 52, 842-857 (1996).
61. Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).
62. Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307-321 (2010).