Structural and thermodynamic basis of epitope binding by neutralizing and nonneutralizing forms of the anti-HIV-1 antibody 4E10

Journal of Virology

Volumn 89, Issue 23, 2015, Pages 11975-11989

  Rujas, Edurne ^a,b   Gulzar, Naveed ^c   Morante, Koldo ^a   Tsumoto, Kouhei ^a   Scott, Jamie K ^c   Nieva, José L ^b   Caaveiro, Jose M M ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b CSIC UPV Unidad de Biofisica UBF   (Spain)

^c SIMON FRASER UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; MONOCLONAL ANTIBODY 4E10; TRYPTOPHAN; 4E10 MONOCLONAL ANTIBODY; GLYCOPROTEIN GP 41; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; PROTEIN BINDING;

ANTIBODY AND IMMUNOGLOBULIN STRUCTURE; ARTICLE; BINDING AFFINITY; BINDING ASSAY; COMPLEMENTARITY DETERMINING REGION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROPHOBICITY; MEMBRANE PROXIMAL EXTERNAL REGION; MOLECULAR DYNAMICS; PHASE TRANSITION; PRIORITY JOURNAL; RESIDUE ANALYSIS; SEQUENCE ANALYSIS; STRUCTURE ANALYSIS; THERMODYNAMICS; CHEMISTRY; CRYSTALLIZATION; DIFFERENTIAL SCANNING CALORIMETRY; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; METABOLISM; MOLECULAR MODEL; SERODIAGNOSIS; SURFACE PLASMON RESONANCE; X RAY DIFFRACTION;

ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; CALORIMETRY, DIFFERENTIAL SCANNING; CRYSTALLIZATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITOPES; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP41; HUMANS; MODELS, MOLECULAR; NEUTRALIZATION TESTS; PROTEIN BINDING; SURFACE PLASMON RESONANCE; THERMODYNAMICS; X-RAY DIFFRACTION;

EID: 84949673021     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01793-15     Document Type: Article

References (57)

1. Salzwedel K, West JT, Hunter E. 1999. A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. J Virol 73:2469-2480.
2. Apellaniz B, Ivankin A, Nir S, Gidalevitz D, Nieva JL. 2011. Membraneproximal external HIV-1 gp41 motif adapted for destabilizing the highly rigid viral envelope. Biophys J 101:2426-2435. http://dx.doi.org/10.1016/j.bpj.2011.10.005.
3. Apellaniz B, Rujas E, Carravilla P, Requejo-Isidro J, Huarte N, Domene C, Nieva JL. 2014. Cholesterol-dependent membrane fusion induced by the gp41 membrane-proximal external region-transmembrane domain connection suggests a mechanism for broad HIV-1 neutralization. J Virol 88:13367-13377. http://dx.doi.org/10.1128/JVI.02151-14.
4. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, Imamichi H, Bailer RT, Chakrabarti B, Sharma SK, Alam SM, Wang T, Yang Y, Zhang B, Migueles SA, Wyatt R, Haynes BF, Kwong PD, Mascola JR, Connors M. 2012. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491:406-412. http://dx.doi.org/10.1038/nature11544.
5. Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos CJ, Burton DR. 2004. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78:13232-13252. http://dx.doi.org/10.1128/JVI.78.23.13232-13252.2004.
6. Kwong PD, Mascola JR. 2012. Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37:412-425. http://dx.doi.org/10.1016/j.immuni.2012.08.012.
7. Burton DR, Desrosiers RC, Doms RW, KoffWC, Kwong PD, Moore JP, Nabel GJ, Sodroski J, Wilson IA, Wyatt RT. 2004. HIV vaccine design and the neutralizing antibody problem. Nat Immunol 5:233-236. http://dx.doi.org/10.1038/ni0304-233.
8. Zwick MB. 2005. The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring. AIDS 19:1725-1737. http://dx.doi.org/10.1097/01.aids.0000189850.83322.41.
9. Montero M, van Houten NE, Wang X, Scott JK. 2008. The membraneproximal 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. http://dx.doi.org/10.1128/MMBR.00020-07.
10. Cardoso RM, Zwick MB, Stanfield RL, Kunert R, Binley JM, Katinger H, Burton DR, Wilson IA. 2005. Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusionassociated motif in gp41. Immunity 22:163-173. http://dx.doi.org/10.1016/j.immuni.2004.12.011.
11. Cardoso RM, Brunel FM, Ferguson S, Zwick M, Burton DR, Dawson PE, Wilson IA. 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. http://dx.doi.org/10.1016/j.jmb.2006.10.088.
12. Brunel FM, Zwick MB, Cardoso RMF, Nelson JD, Wilson IA, Burton DR, Dawson PE. 2006. Structure-function analysis of the epitope for 4E10, a broadly neutralizing human immunodeficiency virus type 1 antibody. J Virol 80:1680-1687. http://dx.doi.org/10.1128/JVI.80.4.1680-1687.2006.
13. Bird GH, Irimia A, Ofek G, Kwong PD, Wilson IA, Walensky LD. 2014. Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies. Nat Struct Mol Biol 21:1058-1067. http://dx.doi.org/10.1038/nsmb.2922.
14. Scherer EM, Leaman DP, Zwick MB, McMichael AJ, Burton DR. 2010. Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions. Proc Natl Acad Sci U S A 107:1529-1534. http://dx.doi.org/10.1073/pnas.0909680107.
15. Alam SM, Morelli M, Dennison SM, Liao HX, Zhang R, Xia SM, Rits-Volloch S, Sun L, Harrison SC, Haynes BF, Chen B. 2009. Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci U S A 106:20234-20239. http://dx.doi.org/10.1073/pnas.0908713106.
16. Xu HY, Song LK, Kim M, Holmes MA, Kraft Z, Sellhorn G, Reinherz EL, Stamatatos L, Strong RK. 2010. Interactions between lipids and human anti-HIV antibody 4E10 can be reduced without ablating neutralizing activity. J Virol 84:1076-1088. http://dx.doi.org/10.1128/JVI.02113-09.
17. Finton KA, Larimore K, Larman HB, Friend D, Correnti C, Rupert PB, Elledge SJ, Greenberg PD, Strong RK. 2013. Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation of the anti-HIV antibody 4E10. PLoS Pathog 9:e1003639. http://dx.doi.org/10.1371/journal.ppat.1003639.
18. Finton KA, Friend D, Jaffe J, Gewe M, Holmes MA, Larman HB, Stuart A, Larimore K, Greenberg PD, Elledge SJ, Stamatatos L, Strong RK. 2014. Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10. PLoS Pathog 10:e1004403. http://dx.doi.org/10.1371/journal.ppat.1004403.
19. Apellaniz B, Rujas E, Serrano S, Morante K, Tsumoto K, Caaveiro JMM, Jimenez MA, Nieva JL. 2015. The atomic structure of the HIV-1 gp41 transmembrane domain and its connection to the immunogenic membrane-proximal external region. J Biol Chem 290:12999-13015. http://dx.doi.org/10.1074/jbc. M115.644351.
20. Kiyoshi M, Caaveiro JMM, Miura E, Nagatoishi S, Nakakido M, Soga S, Shirai H, Kawabata S, Tsumoto K. 2014. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex. PLoS One 9:e87099. http://dx.doi.org/10.1371/journal.pone.0087099.
21. Kiyoshi M, Caaveiro JMM, Kawai T, Tashiro S, Ide T, Asaoka Y, Hatayama K, Tsumoto K. 2015. Structural basis for binding of human IgG1 to its high-affinity human receptor Fc[gamma]RI. Nat Commun 6:6866. http://dx.doi.org/10.1038/ncomms7866.
22. Montero M, Gulzar N, Klaric KA, Donald JE, Lepik C, Wu S, Tsai S, Julien JP, Hessell AJ, Wang S, Lu S, Burton DR, Pai EF, Degrado WF, Scott JK. 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. http://dx.doi.org/10.1128/JVI.06349-11.
23. Julien JP, Huarte N, Maeso R, Taneva SG, Cunningham A, Nieva JL, Pai EF. 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.http://dx.doi.org/10.1128/JVI.02357-09.
24. Evans P. 2006. Scaling and assessment of data quality. Acta Crystallogr D 62:72-82. http://dx.doi.org/10.1107/S0907444905036693.
25. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. 2007. Phaser crystallographic software. J Appl Crystallogr 40: 658-674. http://dx.doi.org/10.1107/S0021889807021206.
26. Murshudov GN, Vagin AA, Dodson EJ. 1997. Refinement of macromolecular structures by the maximum-likelihood method. Acta CrystallogrD 53:240-255. http://dx.doi.org/10.1107/S0907444996012255.
27. Emsley P, Lohkamp B, Scott WG, Cowtan K. 2010. Features and development of Coot. Acta Crystallogr D 66:486-501. http://dx.doi.org/10.1107/S0907444910007493.
28. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. 1993. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283-291. http://dx.doi.org/10.1107/S0021889892009944.
29. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, Keegan RM, Krissinel EB, Leslie AGW, McCoy A, McNicholas SJ, Murshudov GN, Pannu NS, Potterton EA, Powell HR, Read RJ, Vagin A, Wilson KS. 2011. Overview of the CCP4 suite and current developments. Acta Crystallogr D 67:235-242. http://dx.doi.org/10.1107/S0907444910045749.
30. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH. 2010. PHENIX: a comprehensive Pythonbased system for macromolecular structure solution. Acta Crystallogr D 66:213-221. http://dx.doi.org/10.1107/S0907444909052925.
31. Gore S, Velankar S, Kleywegt GJ. 2012. Implementing an X-ray validation pipeline for the Protein Data Bank. Acta Crystallogr D 68:478-483. http://dx.doi.org/10.1107/S0907444911050359.
32. Langer G, Cohen SX, Lamzin VS, Perrakis A. 2008. Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7. Nat Protoc 3:1171-1179. http://dx.doi.org/10.1038/nprot.2008.91.
33. Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D, Alber T. 2009. Hidden alternative structures of proline isomerase essential for catalysis. Nature 462:669-673. http://dx.doi.org/10.1038/nature08615.
34. Lang PT, Ng HL, Fraser JS, Corn JE, Echols N, Sales M, Holton JM, Alber T. 2010. Automated electron-density sampling reveals widespread conformational polymorphism in proteins. Protein Sci 19:1420-1431. http://dx.doi.org/10.1002/pro.423.
35. Miyafusa T, Caaveiro JMM, Tanaka Y, Tsumoto K. 2013. Dynamic elements govern the catalytic activity of CapE, a capsular polysaccharidesynthesizing enzyme from Staphylococcus aureus. FEBS Lett 587:3824-3830.http://dx.doi.org/10.1016/j.febslet.2013.10.009.
36. Sakamoto S, Caaveiro JMM, Sano E, Tanaka Y, Kudou M, Tsumoto K. 2009. Contributions of interfacial residues of human interleukin15 to the specificity and affinity for its private α-receptor. J Mol Biol 389:880-894. http://dx.doi.org/10.1016/j.jmb.2009.04.050.
37. Cleland WW, Northrop DB. 1999. Energetics of substrate binding, catalysis, and product release. Methods Enzymol 308:3-27. http://dx.doi.org/10.1016/S0076-6879(99)08003-9.
38. Seaman MS, Janes H, Hawkins N, Grandpre LE, Devoy C, Giri A, Coffey RT, Harris L, Wood B, Daniels MG, Bhattacharya T, Lapedes A, Polonis VR, McCutchan FE, Gilbert PB, Self SG, Korber BT, Montefiori DC, Mascola JR. 2010. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol 84: 1439-1452. http://dx.doi.org/10.1128/JVI.02108-09.
39. Lawrence MC, Colman PM. 1993. Shape complementarity at proteinprotein interfaces. J Mol Biol 234:946-950. http://dx.doi.org/10.1006/jmbi.1993.1648.
40. Klein JS, Gnanapragasam PNP, Galimidi RP, Foglesong CP, West AP, Bjorkman PJ. 2009. Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10. Proc Natl Acad Sci U S A 106:7385-7390. http://dx.doi.org/10.1073/pnas.0811427106.
41. Leaman DP, Lee JH, Ward AB, Zwick MB. 2015. Immunogenic display of purified chemically cross-linked HIV-1 spikes. J Virol 89:6725-6745. http://dx.doi.org/10.1128/JVI.03738-14.
42. Krissinel E, Henrick K. 2007. Inference of macromolecular assemblies from crystalline state. J Mol Biol 372:774-797. http://dx.doi.org/10.1016/j.jmb.2007.05.022.
43. van den Bedem H, Bhabha G, Yang K, Wright PE, Fraser JS. 2013. Automated identification of functional dynamic contact networks from X-ray crystallography. Nat Methods 10:896-U110. http://dx.doi.org/10.1038/nmeth.2592.
44. Jones TA, Zou JY, Cowan SW, Kjeldgaard M. 1991. Improved methods for building protein models in electron-density maps and the location of errors in these models. Acta Crystallogr A 47:110-119. http://dx.doi.org/10.1107/S0108767390010224.
45. Huarte N, Lorizate M, Maeso R, Kunert R, Arranz R, Valpuesta JM, Nieva JL. 2008. The broadly neutralizing anti-human immunodeficiency virus type 1 4E10 monoclonal antibody is better adapted to membranebound epitope recognition and blocking than 2F5. J Virol 82:8986-8996. http://dx.doi.org/10.1128/JVI.00846-08.
46. Lorizate M, Cruz A, Huarte N, Kunert R, Perez-Gil J, Nieva JL. 2006. Recognition and blocking of HIV-1 gp41 pre-transmembrane sequence by monoclonal 4E10 antibody in a raft-like membrane environment. J Biol Chem 281:39598-39606. http://dx.doi.org/10.1074/jbc. M605998200.
47. Sanchez-Martinez S, Lorizate M, Katinger H, Kunert R, Nieva JL. 2006. Membrane association and epitope recognition by HIV-1 neutralizing anti-gp41 2F5 and 4E10 antibodies. AIDS Res Hum Retroviruses 22:998-1006.http://dx.doi.org/10.1089/aid.2006.22.998.
48. Sun ZY, Oh KJ, Kim M, Yu J, Brusic V, Song L, Qiao Z, Wang JH, Wagner G, Reinherz EL. 2008. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity 28:52-63. http://dx.doi.org/10.1016/j.immuni.2007.11.018.
49. Ofek G, McKee K, Yang YP, Yang ZY, Skinner J, Guenaga FJ, Wyatt R, Zwick MB, Nabel GJ, Mascola JR, Kwong PD. 2010. Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region. J Virol 84:2955-2962.http://dx.doi.org/10.1128/JVI.02257-09.
50. Burton DR, Mascola JR. 2015. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat Immunol 16:571-576. http://dx.doi.org/10.1038/ni.3158.
51. Klein F, Mouquet H, Dosenovic P, Scheid JF, Scharf L, Nussenzweig MC. 2013. Antibodies in HIV-1 vaccine development and therapy. Science 341:1199-1204. http://dx.doi.org/10.1126/science.1241144.
52. Muster T, Steindl F, Purtscher M, Trkola A, Klima A, Himmler G, Ruker F, Katinger H. 1993. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67:6642-6647.
53. Muster T, Guinea R, Trkola A, Purtscher M, Klima A, Steindl F, Palese P, 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.
54. Purtscher M, Trkola A, Gruber G, Buchacher A, Predl R, Steindl F, Tauer C, Berger R, Barrett N, Jungbauer A, et al. 1994. A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 10:1651-1658. http://dx.doi.org/10.1089/aid.1994.10.1651.
55. Stiegler G, Kunert R, Purtscher M, Wolbank S, Voglauer R, Steindl F, Katinger H. 2001. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 17:1757-1765. http://dx.doi.org/10.1089/08892220152741450.
56. Kunert R, Ruker F, Katinger H. 1998. Molecular characterization of five neutralizing anti-HIV type 1 antibodies: identification of nonconventional D segments in the human monoclonal antibodies 2G12 and 2F5. AIDS ResHumRetroviruses 14:1115-1128. http://dx.doi.org/10.1089/aid.1998.14.1115.
57. Wallace AC, Laskowski RA, Thornton JM. 1995. Ligplot: a program to generate schematic diagrams of protein ligand interactions. Prot Eng 8:127-134. http://dx.doi.org/10.1093/protein/8.2.127.