Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans

PLoS Pathogens

Volumn 9, Issue 5, 2013, Pages

  Julien, Jean Philippe ^a   Sok, Devin ^a   Khayat, Reza ^a   Lee, Jeong Hyun ^a   Doores, Katie J ^a   Walker, Laura M ^a   Ramos, Alejandra ^a   Diwanji, Devan C ^a   Pejchal, Robert ^a   Cupo, Albert ^b   Katpally, Umesh ^b   Depetris, Rafael S ^b   Stanfield, Robyn L ^a   McBride, Ryan ^a   Marozsan, Andre J ^b   Paulson, James C ^a   Sanders, Rogier W ^b,c   Moore, John P ^b   Burton, Dennis R ^a,d   Poignard, Pascal ^a   Ward, Andrew B ^a   Wilson, Ian A ^a   more..

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c ACADEMIC MEDICAL CENTER   (Netherlands)

^d MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; GLYCAN; GLYCOPROTEIN GP 120; NEUTRALIZING ANTIBODY; NEUTRALIZING ANTIBODY PGT121; UNCLASSIFIED DRUG;

ANTIBODY COMBINING SITE; ANTIGEN BINDING; ARTICLE; CRYSTALLIZATION; ELECTRON MICROSCOPY; ENANTIOMER; FLOW CYTOMETRY; GEL PERMEATION CHROMATOGRAPHY; HUMAN; HUMAN CELL; IC 50; ION EXCHANGE CHROMATOGRAPHY; ISOTHERMAL TITRATION CALORIMETRY; PREVALENCE; PROTEIN EXPRESSION; PROTEIN MICROARRAY; PROTEIN PURIFICATION; SEQUENCE ALIGNMENT; SITE DIRECTED MUTAGENESIS; X RAY DIFFRACTION;

ALLOSTERIC REGULATION; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; ANTIGENS, CD4; BINDING SITES, ANTIBODY; CRYSTALLOGRAPHY, X-RAY; EPITOPES; GLYCOPROTEINS; HEK293 CELLS; HIV ENVELOPE PROTEIN GP120; HIV-1; HUMANS; IMMUNOGLOBULIN HEAVY CHAINS; PROTEIN STRUCTURE, QUATERNARY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84878519611     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003342     Document Type: Article

References (75)

1. Kwong PD, Mascola JR, Nabel GJ, (2009) Mining the B cell repertoire for broadly neutralizing monoclonal antibodies to HIV-1. Cell Host Microbe 6: 292-294.
2. Mouquet H, Klein F, Scheid JF, Warncke M, Pietzsch J, et al. (2011) Memory B cell antibodies to HIV-1 gp140 cloned from individuals infected with clade A and B viruses. PLoS One 6: e24078.
3. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, et al. (2011) Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333: 1633-1637.
4. Simek MD, Rida W, Priddy FH, Pung P, Carrow E, et al. (2009) Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol 83: 7337-7348.
5. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, et al. (2011) Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477: 466-470.
6. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, et al. (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326: 285-289.
7. Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, et al. (2011) Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science 333: 1593-1602.
8. Kwong PD, Mascola JR, (2012) Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37: 412-425.
9. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, et al. (2012) Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491: 406-412.
10. Wang Y, Keck ZY, Foung SK, (2011) Neutralizing antibody response to hepatitis C virus. Viruses 3: 2127-2145.
11. Ekiert DC, Friesen RH, Bhabha G, Kwaks T, Jongeneelen M, et al. (2011) A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 333: 843-850.
12. Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, et al. (2011) A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333: 850-856.
13. Dreyfus C, Laursen NS, Kwaks T, Zuijdgeest D, Khayat R, et al. (2012) Highly conserved protective epitopes on influenza B viruses. Science 337: 1343-1348.
14. Doria-Rose NA, Klein RM, Manion MM, O'Dell S, Phogat A, et al. (2009) Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol 83: 188-199.
15. Sather DN, Armann J, Ching LK, Mavrantoni A, Sellhorn G, et al. (2009) Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol 83: 757-769.
16. Stamatatos L, Morris L, Burton DR, Mascola JR, (2009) Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat Med 15: 866-870.
17. Walker LM, Simek MD, Priddy F, Gach JS, Wagner D, et al. (2010) A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS Pathog 6: e1001028.
18. Overbaugh J, Morris L, (2012) The antibody response against HIV-1. Cold Spring Harb Perspect Med 2: a007039.
19. Gray ES, Madiga MC, Hermanus T, Moore PL, Wibmer CK, et al. (2011) The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. J Virol 85: 4828-4840.
20. Klein F, Gaebler C, Mouquet H, Sather DN, Lehmann C, et al. (2012) Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein. J Exp Med 209: 1469-1479.
21. Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, et al. (2010) Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329: 811-817.
22. Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, et al. (2011) Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol 85: 9998-10009.
23. Bonomelli C, Doores KJ, Dunlop DC, Thaney V, Dwek RA, et al. (2011) The glycan shield of HIV is predominantly oligomannose independently of production system or viral clade. PLoS One 6: e23521.
24. Doores KJ, Bonomelli C, Harvey DJ, Vasiljevic S, Dwek RA, et al. (2010) Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci U S A 107: 13800-13805.
25. Go EP, Chang Q, Liao HX, Sutherland LL, Alam SM, et al. (2009) Glycosylation site-specific analysis of clade C HIV-1 envelope proteins. J Proteome Res 8: 4231-4242.
26. Go EP, Hewawasam G, Liao HX, Chen H, Ping LH, et al. (2011) Characterization of glycosylation profiles of HIV-1 transmitted/founder envelopes by mass spectrometry. J Virol 85: 8270-8284.
27. Scanlan CN, Pantophlet R, Wormald MR, Ollmann Saphire E, Stanfield R, et al. (2002) The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1→2 mannose residues on the outer face of gp120. J Virol 76: 7306-7321.
28. Calarese DA, Scanlan CN, Zwick MB, Deechongkit S, Mimura Y, et al. (2003) Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300: 2065-2071.
29. Pejchal R, Doores KJ, Walker LM, Khayat R, Huang PS, et al. (2011) A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334: 1097-1103.
30. Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, et al. (2012) Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A 109: E3268-3277.
31. Krissinel E, Henrick K, (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372: 774-797.
32. Depetris RS, Julien JP, Khayat R, Lee JH, Pejchal R, et al. (2012) Partial enzymatic deglycosylation preserves the structure of cleaved recombinant HIV-1 envelope glycoprotein trimers. J Biol Chem 287: 24239-24254.
33. Sanders RW, Vesanen M, Schuelke N, Master A, Schiffner L, et al. (2002) Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol 76: 8875-8889.
34. Stanfield RL, Zemla A, Wilson IA, Rupp B, (2006) Antibody elbow angles are influenced by their light chain class. J Mol Biol 357: 1566-1574.
35. Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S, (2008) Molecular architecture of native HIV-1 gp120 trimers. Nature 455: 109-113.
36. Falkowska E, Ramos A, Feng Y, Zhou T, Moquin S, et al. (2012) PGV04, an HIV-1 gp120 CD4 binding site antibody, is broad and potent in neutralization but does not induce conformational changes characteristic of CD4. J Virol 86: 4394-4403.
37. Madani N, Schon A, Princiotto AM, Lalonde JM, Courter JR, et al. (2008) Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120. Structure 16: 1689-1701.
38. Zhao Q, Ma L, Jiang S, Lu H, Liu S, et al. (2005) Identification of N-phenyl-N′-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4. Virology 339: 213-225.
39. Kwon YD, Finzi A, Wu X, Dogo-Isonagie C, Lee LK, et al. (2012) Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops. Proc Natl Acad Sci U S A 109: 5663-5668.
40. Moore JP, McKeating JA, Huang YX, Ashkenazi A, Ho DD, (1992) Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol 66: 235-243.
41. Mulligan MJ, Ritter GD Jr, Chaikin MA, Yamshchikov GV, Kumar P, et al. (1992) Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex. Virology 187: 233-241.
42. Kim M, Chen B, Hussey RE, Chishti Y, Montefiori D, et al. (2001) The stoichiometry of trimeric SIV glycoprotein interaction with CD4 differs from that of anti-envelope antibody Fab fragments. J Biol Chem 276: 42667-42676.
43. Kovacs JM, Nkolola JP, Peng H, Cheung A, Perry J, et al. (2012) HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. Proc Natl Acad Sci U S A 109: 12111-12116.
44. Dey B, Svehla K, Xu L, Wycuff D, Zhou T, et al. (2009) Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog 5: e1000445.
45. McLellan JS, Pancera M, Carrico C, Gorman J, Julien JP, et al. (2011) Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 23: 336-343.
46. Platt EJ, Gomes MM, Kabat D, (2012) Kinetic mechanism for HIV-1 neutralization by antibody 2G12 entails reversible glycan binding that slows cell entry. Proc Natl Acad Sci U S A 109: 7829-7834.
47. Trkola A, Dragic T, Arthos J, Binley JM, Olson WC, et al. (1996) CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 384: 184-187.
48. Garlick RL, Kirschner RJ, Eckenrode FM, Tarpley WG, Tomich CS, (1990) Escherichia coli expression, purification, and biological activity of a truncated soluble CD4. AIDS Res Hum Retroviruses 6: 465-479.
49. Pejchal R, Walker LM, Stanfield RL, Phogat SK, Koff WC, et al. (2010) Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1. Proc Natl Acad Sci U S A 107: 11483-11488.
50. Klock HE, Lesley SA, (2009) The Polymerase Incomplete Primer Extension (PIPE) method applied to high-throughput cloning and site-directed mutagenesis. Methods Mol Biol 498: 91-103.
51. Ekiert DC, Kashyap AK, Steel J, Rubrum A, Bhabha G, et al. (2012) Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489: 526-532.
52. Kabsch W, (2010) Xds. Acta Crystallogr D Biol Crystallogr 66: 125-132.
53. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, et al. (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658-674.
54. Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, et al. (1998) Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr 54: 905-921.
55. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, et al. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr 67: 235-242.
56. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213-221.
57. Emsley P, Cowtan K, (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126-2132.
58. Li M, Gao F, Mascola JR, Stamatatos L, Polonis VR, et al. (2005) Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol 79: 10108-10125.
59. Doores KJ, Burton DR, (2010) Variable loop glycan dependency of the broad and potent HIV-1-neutralizing antibodies PG9 and PG16. J Virol 84: 10510-10521.
60. Blixt O, Head S, Mondala T, Scanlan C, Huflejt ME, et al. (2004) Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci U S A 101: 17033-17038.
61. Xu R, McBride R, Nycholat CM, Paulson JC, Wilson IA, (2012) Structural characterization of the hemagglutinin receptor specificity from the 2009 H1N1 influenza pandemic. J Virol 86: 982-990.
62. Nycholat CM, McBride R, Ekiert DC, Xu R, Rangarajan J, et al. (2012) Recognition of sialylated poly-N-acetyllactosamine chains on N- and O-linked glycans by human and avian influenza A virus hemagglutinins. Angew Chem Int Ed Engl 51: 4860-4863.
63. Suloway C, Pulokas J, Fellmann D, Cheng A, Guerra F, et al. (2005) Automated molecular microscopy: the new Leginon system. J Struct Biol 151: 41-60.
64. Voss NR, Yoshioka CK, Radermacher M, Potter CS, Carragher B, (2009) DoG Picker and TiltPicker: software tools to facilitate particle selection in single particle electron microscopy. J Struct Biol 166: 205-213.
65. Mindell JA, Grigorieff N, (2003) Accurate determination of local defocus and specimen tilt in electron microscopy. J Struct Biol 142: 334-347.
66. Hohn M, Tang G, Goodyear G, Baldwin PR, Huang Z, et al. (2007) SPARX, a new environment for Cryo-EM image processing. J Struct Biol 157: 47-55.
67. Tang G, Peng L, Baldwin PR, Mann DS, Jiang W, et al. (2007) EMAN2: an extensible image processing suite for electron microscopy. J Struct Biol 157: 38-46.
68. Sorzano CO, Bilbao-Castro JR, Shkolnisky Y, Alcorlo M, Melero R, et al. (2010) A clustering approach to multireference alignment of single-particle projections in electron microscopy. J Struct Biol 171: 197-206.
69. Vagin A, Teplyakov A, (2010) Molecular replacement with MOLREP. Acta Crystallogr D Biol Crystallogr 66: 22-25.
70. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, et al. (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612.
71. Gasteiger EHC, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A, (2005) Protein Identification and Analysis Tools on the ExPASy Server. In: The Proteomics Protocols Handbook Walker JM, editor. Humana Press. pp. 571-607.
72. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ, (2009) Jalview Version 2-a multiple sequence alignment editor and analysis workbench. Bioinformatics 25: 1189-1191.
73. Matthews BW, (1968) Solvent content of protein crystals. J Mol Biol 33: 491-497.
74. Kantardjieff KA, Rupp B, (2003) Matthews coefficient probabilities: Improved estimates for unit cell contents of proteins, DNA, and protein-nucleic acid complex crystals. Protein Sci 12: 1865-1871.
75. de Azevedo WF Jr, Dias R, (2008) Experimental approaches to evaluate the thermodynamics of protein-drug interactions. Curr Drug Targets 9: 1071-1076.