Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5

Proteins: Structure, Function and Bioinformatics

Volumn 82, Issue 10, 2014, Pages 2770-2782

  Azoitei, M L ^a,d   Ban, Y A ^a,e   Kalyuzhny, O ^a,b   Guenaga, J ^b   Schroeter, A ^a   Porter, J ^a   Wyatt, R ^b   Schief, William R ^a,b,c  

^a UNIVERSITY OF WASHINGTON   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^d UNIVERSITY OF NORTH CAROLINA   (United States)

^e Arzeda Corporation   (United States)

Author keywords

Antigen; Epitope scaffold; Flexible backbone design; Grafting

Indexed keywords

EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; NEUTRALIZING ANTIBODY; NEUTRALIZING ANTIBODY 2F5; SCAFFOLD PROTEIN; UNCLASSIFIED DRUG; 2F5 MONOCLONAL ANTIBODY; ANTIGEN; COMPLEMENTARITY DETERMINING REGION; HUMAN IMMUNODEFICIENCY VIRUS PROTEIN; MONOCLONAL ANTIBODY; PEPTIDE LIBRARY; RECOMBINANT PROTEIN; VIRUS ANTIBODY;

ADULT; ALGORITHM; ANTIBODY ENGINEERING; ANTIBODY RESPONSE; ANTIBODY SPECIFICITY; ANTIBODY STRUCTURE; ANTIBODY TITER; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; BINDING KINETICS; CDR H3 LOOP; CLINICAL FEATURE; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME LINKED IMMUNOSORBENT ASSAY; EXPERIMENTAL RABBIT; FEMALE; GEL PERMEATION CHROMATOGRAPHY; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROPHOBICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN STRUCTURE; AMINO ACID SEQUENCE; ANIMAL; ANTAGONISTS AND INHIBITORS; ANTIBODY AFFINITY; BIOLOGY; CHEMICAL STRUCTURE; CHEMISTRY; COMPARATIVE STUDY; COMPLEMENTARITY DETERMINING REGION; COMPUTER PROGRAM; GENETICS; INTERNET; METABOLISM; MOLECULAR GENETICS; PEPTIDE LIBRARY; PROTEIN ENGINEERING;

HUMAN IMMUNODEFICIENCY VIRUS 1;

AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; ANTIBODY AFFINITY; ANTIBODY SPECIFICITY; ANTIGENS; COMPLEMENTARITY DETERMINING REGIONS; COMPUTATIONAL BIOLOGY; EPITOPES; HUMAN IMMUNODEFICIENCY VIRUS PROTEINS; INTERNET; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PEPTIDE LIBRARY; PROTEIN CONFORMATION; PROTEIN ENGINEERING; RECOMBINANT PROTEINS; SOFTWARE;

EID: 84937730760     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.24641     Document Type: Article

References (39)

1. Rani M, Bolles M, Donaldson EF, Van Blarcom T, Baric R, Iverson B, Georgiou G. Increased antibody affinity confers broad in vitro protection against escape mutants of severe acute respiratory syndrome coronavirus. J Virol 2012;86:9113-9121.
2. Gilbreth RN, Koide S. Structural insights for engineering binding proteins based on non-antibody scaffolds. Curr Opin Struct Biol 2012;22:413-420.
3. Hackel BJ, Kapila A, Wittrup KD. Picomolar affinity fibronectin domains engineered utilizing loop length diversity, recursive mutagenesis, and loop shuffling. J Mol Biol 2008;381:1238-1252.
4. Fleishman SJ, Whitehead TA, Ekiert DC, Dreyfus C, Corn JE, Strauch EM, Wilson IA, Baker D. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science 2011;332:816-821.
5. Correia BE, Ban YE, Holmes MA, Xu H, Ellingson K, Kraft Z, Carrico C, Boni E, Sather DN, Zenobia C, Burke KY, Bradley-Hewitt T, Bruhn-Johannsen JF, Kalyuzhniy O, Baker D, Strong RK, Stamatatos L, Schief WR. Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope. Structure 2010;18:1116-1126.
6. Azoitei ML, Correia BE, Ban YE, Carrico C, Kalyuzhniy O, Chen L, Schroeter A, Huang PS, McLellan JS, Kwong PD, Baker D, Strong RK, Schief WR. Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. Science 2011;334:373-376.
7. Correia BE, Bates JT, Loomis RJ, Baneyx G, Carrico C, Jardine JG, Rupert P, Correnti C, Kalyuzhniy O, Vittal V, Connell MJ, Stevens E, Schroeter A, Chen M, Macpherson S, Serra AM, Adachi Y, Holmes MA, Li Y, Klevit RE, Graham BS, Wyatt RT, Baker D, Strong RK, Crowe JE Jr, Johnson PR, Schief WR. Proof of principle for epitope-focused vaccine design. Nature 2014;507:201-206.
8. Azoitei ML, Ban YE, Julien JP, Bryson S, Schroeter A, Kalyuzhniy O, Porter JR, Adachi Y, Baker D, Pai EF, Schief WR. Computational design of high-affinity epitope scaffolds by backbone grafting of a linear epitope. J Mol Biol 2012;415:175-192.
9. Das R, Baker D. Macromolecular modeling with rosetta. Annu Rev Biochem 2008;77:363-382.
10. Leaver-Fay A, Tyka M, Lewis SM, Lange OF, Thompson J, Jacak R, Kaufman K, Renfrew PD, Smith CA, Sheffler W, Davis IW, Cooper S, Treuille A, Mandell DJ, Richter F, Ban YE, Fleishman SJ, Corn JE, Kim DE, Lyskov S, Berrondo M, Mentzer S, Popovic Z, Havranek JJ, Karanicolas J, Das R, Meiler J, Kortemme T, Gray JJ, Kuhlman B, Baker D, Bradley P. ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods Enzymol 2011;487:545-574.
11. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res 2000;28:235-242.
12. Ofek G, Guenaga FJ, Schief WR, Skinner J, Baker D, Wyatt R, Kwong PD. Elicitation of structure-specific antibodies by epitope scaffolds. Proc Natl Acad Sci USA 2010;107:17880-17887.
13. McLellan JS, Correia BE, Chen M, Yang Y, Graham BS, Schief WR, Kwong PD. Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus. J Mol Biol 2011;409:853-866.
14. Kulp DW, Schief WR. Advances in structure-based vaccine design. Curr Opin Virol 2013;3:322-331.
15. Yang G, Holl TM, Liu Y, Li Y, Lu X, Nicely NI, Kepler TB, Alam SM, Liao HX, Cain DW, Spicer L, VandeBerg JL, Haynes BF, Kelsoe G. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J Exp Med 2013;210:241-256.
16. 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. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 2012;491:406-412.
17. Alam SM, Morelli M, Dennison SM, Liao HX, Zhang R, Xia SM, Rits-Volloch S, Sun L, Harrison SC, Haynes BF, Chen B. Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci USA 2009;106:20234-20239.
18. Li Y, O'Dell S, Wilson R, Wu X, Schmidt SD, Hogerkorp CM, Louder MK, Longo NS, Poulsen C, Guenaga J, Chakrabarti BK, Doria-Rose N, Roederer M, Connors M, Mascola JR, Wyatt RT. HIV-1 neutralizing antibodies display dual recognition of the primary and coreceptor binding sites and preferential binding to fully cleaved envelope glycoproteins. J Virol 2012;86:11231-11241.
19. Garcia-Ortiz L, Recio-Rodriguez JI, Canales-Reina JJ, Cabrejas-Sanchez A, Gomez-Arranz A, Magdalena-Belio JF, Guenaga-Saenz N, Agudo-Conde C, Gomez-Marcos MA, Group E. Comparison of two measuring instruments, B-pro and SphygmoCor system as reference, to evaluate central systolic blood pressure and radial augmentation index. Hypertens Res 2012;35:617-623.
20. Ofek G, McKee K, Yang Y, Yang ZY, Skinner J, Guenaga FJ, Wyatt R, Zwick MB, Nabel GJ, Mascola JR, Kwong PD. Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region. J Virol 2010;84:2955-2962.
21. Julien JP, Huarte N, Maeso R, Taneva SG, Cunningham A, Nieva JL, Pai EF. 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 2010;84:4136-4147.
22. Gray JJ, Moughon S, Wang C, Schueler-Furman O, Kuhlman B, Rohl CA, Baker D. Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol 2003;331:281-299.
23. Chao G, Lau WL, Hackel BJ, Sazinsky SL, Lippow SM, Wittrup KD. Isolating and engineering human antibodies using yeast surface display. Nat Protoc 2006;1:755-768.
24. Krissinel E, Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol 2007;372:774-797.
25. Nevskaya N, Tishchenko S, Paveliev M, Smolinskaya Y, Fedorov R, Piendl W, Nakamura Y, Toyoda T, Garber M, Nikonov S. Structure of ribosomal protein L1 from Methanococcus thermolithotrophicus. Functionally important structural invariants on the L1 surface. Acta Crystallogr D Biol Crystallogr 2002;58:1023-1029.
26. Hickman AB, Li Y, Mathew SV, May EW, Craig NL, Dyda F. Unexpected structural diversity in DNA recombination: the restriction endonuclease connection. Mol Cell 2000;5:1025-1034.
27. Markovic-Housley Z, Miglierini G, Soldatova L, Rizkallah PJ, Muller U, Schirmer T. Crystal structure of hyaluronidase, a major allergen of bee venom. Structure 2000;8:1025-1035.
28. Wang X, He X, Lin J, Shao H, Chang Z, Dixon RA. Crystal structure of isoflavone reductase from alfalfa (Medicago sativa L.). J Mol Biol 2006;358:1341-1352.
29. Julien JP, Bryson S, Nieva JL, Pai EF. Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion-binding site. J Mol Biol 2008;384:377-392.
30. Guenaga J, Wyatt RT. Structure-guided alterations of the gp41-directed HIV-1 broadly neutralizing antibody 2F5 reveal new properties regarding its neutralizing function. PLoS Pathog 2012;8:e1002806.
31. Guenaga J, Dosenovic P, Ofek G, Baker D, Schief WR, Kwong PD, Hedestam GBK, Wyatt RT. Heterologous epitope-scaffold prime:boosting immuno-focuses B cell responses to the HIV-1 gp41 2F5 neutralization determinant. PLoS One 2011;6.
32. Guenaga J, Dosenovic P, Ofek G, Baker D, Schief WR, Kwong PD, Karlsson Hedestam GB, Wyatt RT. Heterologous epitope-scaffold prime:boosting immuno-focuses B cell responses to the HIV-1 gp41 2F5 neutralization determinant. PLoS One 2011;6:e16074.
33. Jha RK, Leaver-Fay A, Yin S, Wu Y, Butterfoss GL, Szyperski T, Dokholyan NV, Kuhlman B. Computational design of a PAK1 binding protein. J Mol Biol 2010;400:257-270.
34. Mandell DJ, Kortemme T. Backbone flexibility in computational protein design. Curr Opin Biotechnol 2009;20:420-428.
35. Karanicolas J, Kuhlman B. Computational design of affinity and specificity at protein-protein interfaces. Curr Opin Struct Biol 2009;19:458-463.
36. Lewis SM, Kuhlman BA. Anchored design of protein-protein interfaces. PLoS One 2011;6:e20872.
37. Stranges PB, Kuhlman B. A comparison of successful and failed protein interface designs highlights the challenges of designing buried hydrogen bonds. Protein Sci 2013;22:74-82.
38. Ofek G, Tang M, Sambor A, Katinger H, Mascola JR, Wyatt R, Kwong PD. Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J Virol 2004;78:10724-10737.
39. Kim M, Sun ZY, Rand KD, Shi X, Song L, Cheng Y, Fahmy AF, Majumdar S, Ofek G, Yang Y, Kwong PD, Wang JH, Engen JR, Wagner G, Reinherz EL. Antibody mechanics on a membrane-bound HIV segment essential for GP41-targeted viral neutralization. Nat Struct Mol Biol 2011;18:1235-1243.