Antibody multispecificity mediated by conformational diversity

Science

Volumn 299, Issue 5611, 2003, Pages 1362-1367

  James, Leo C ^a   Roversi, Pietro ^b   Tawfik, Dan S ^c  

^a MEDICAL RESEARCH COUNCIL   (United Kingdom)

^b GLOBAL PHASING LTD   (United Kingdom)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGENS; ISOMERIZATION; ISOMERS; REACTION KINETICS; X RAY CRYSTALLOGRAPHY;

AROMATIC LIGANDS;

ANTIBODIES;

ANTIGEN; HAPTEN; LIGAND;

ANTIBODY; BIOLOGY;

ALLERGY; ANTIBODY SPECIFICITY; ANTIGEN BINDING; ARTICLE; AUTOIMMUNITY; BINDING AFFINITY; BINDING SITE; BIODIVERSITY; CONFORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; EQUILIBRIUM CONSTANT; ISOMERISM; PRIORITY JOURNAL; PROTEIN ANALYSIS; STEADY STATE; X RAY CRYSTALLOGRAPHY;

2,4-DINITROPHENOL; AMINO ACID SEQUENCE; ANTIBODIES, MONOCLONAL; ANTIBODY DIVERSITY; ANTIBODY SPECIFICITY; ANTIGEN-ANTIBODY COMPLEX; ANTIGEN-ANTIBODY REACTIONS; ANTIGENS; BINDING SITES, ANTIBODY; CROSS REACTIONS; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; DIMERIZATION; HAPTENS; HYDROGEN BONDING; IMMUNOGLOBULIN E; IMMUNOGLOBULIN FRAGMENTS; ISOMERISM; KINETICS; LIGANDS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PEPTIDE LIBRARY; PROTEIN CONFORMATION; RECOMBINANT PROTEINS;

EID: 0037470496     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1079731     Document Type: Article

References (44)

1. L Pauling, J. Am. Chem. Soc. 62, 2643 (1940).
2. K. Landsteiner, Wein. Klin. Wochenschr. 10, 439 (1897).
3. P. Ehrlich, J. Morgenroth, Berl. Klin. Wochenschr. 38, 569 (1901).
4. R. B. Christian, R. N. Zuckermann, J. M. Kerr, L. Wang, B. A. Malcolm, J. Mol. Biol. 227, 711 (1992).
5. J. M. Varga, G. Kalchschmid, G. F. Klein, P. Fritsch, Mol. Immunol. 28, 641 (1991).
6. A. Kramer et al., Cell 91, 799 (1997).
7. M. H. Kaplan, M. Meyeserian, Lancet 1, 706 (1962).
8. M. B. Oldstone, FASEB J. 12, 1255 (1998).
9. S. Vieths, S. Scheurer, B. Ballmer-Weber, Ann. N.Y. Acad. Sci. 964, 47 (2002).
10. M. L. Santiago et al., Int. Arch. Allergy Immunol. 117, 94 (1998).
11. J. H. Arevalo et al., J. Mol. Biol. 241, 663 (1994).
12. C. H. Trinh, S. D. Hemmington, M. E. Verhoeyen, S. E. Phillips, Structure 5, 937 (1997).
13. B. A. Fields, F. A. Goldbaum, X. Ysern, R. J. Poljak, R. A. Mariuzza, Nature 374, 739 (1995).
14. I. A. Wilson, R. L. Stanfield, Curr. Opin. Struct. Biol. 4, 857 (1994).
15. F. E. Romesberg, B. Spiller, P. G. Schultz, R. C. Stevens, Science 279, 1929 (1998).
16. D. Lancet, I. Pecht, Proc. Natl. Acad. Sci. U.S.A. 73, 3549 (1976).
17. J. Foote, C. Milstein, Proc. Natl. Acad. Sci. U.S.A. 91, 10370 (1994).
18. Z. Eshhar, M. Ofarim, T. Waks, J. Immunol. 124, 775 (1980).
19. Materials and methods are available as supporting material on Science Online.
20. The sequence of SPE7 is most similar to IgG antibody B1-8 to NP (19) (fig. S1). The experiments were performed primarily with the recombinant Fv fragment of SPE7 Fv cloned from complementary DNA of the SPE7.49 hybridoma (18) and expressed in Escherichia coli [(19), section 1].
21. Pre-steady-state kinetics were performed and analyzed essentially as described (31); further details are given in section 2 of (19).
22. L. James, D. Tawfik. in preparation.
23. Z. Lu et al., Biotechnology 13, 366 (1995).
24. F. D. Batista, M. S. Neuberger, Immunity 8, 751 (1998).
25. A. V. Collis, A. P. Brouwer, A. C. Martin, J. Mol. Biol. 325, 337 (2003).
26. A. L. Corper et al., Nature Struct. Biol. 4, 374 (1997).
27. K. Asai et al., Immunity 14, 791 (2001).
28. J. Kalesnikoff et al., Immunity 14, 801 (2001).
29. G. J. Wedemayer, P. A. Patten, L. H. Wang, P. G. Schultz, R. C. Stevens, Science 276, 1665 (1997).
30. I. A. Wilson, R. A. Stanfield, Curr. Opin. Struct. Biol. 4, 857 (1994).
31. A. B. Lindner, Z. Eshhar, D. S. Tawfik, J. Mol. Biol. 285, 421 (1999).
32. B. F. Volkmanm, D. Lipson, D. E. Wemmer, D. Kern, Science 291, 2429 (2001).
33. G. F. Joyce, Science 276, 1658 (1997).
34. B. Ma, M. Shatsky, H. J. Wolfson, R. Nussinov, Protein Sci. 11, 184 (2002).
35. P. E. Wright, H. J. Dyson, J. Mol. Biol. 293, 321 (1999).
36. T. K. Hitchens, B. Mannervik, G. S. Rule, Biochemistry 40, 11660 (2001).
37. Crystals were grown under the conditions described in Table 1. Details regarding crystal structure determination and additional data are given in section 3 of (19), including a Ramanchandran plot (fig. S2), electron density maps (fig. S3), B values (table S1), and a list of the interactions between SPE7 and the various ligands (table S2).
38. Collaborative Computational Project, No. 4, version 4.2, Acta. Cryst. D50, 760 (1994).
39. A. Nicholls, K. Sharp, B. Honig, Proteins Struct. Funct. Genet. 11, 281 (1991).
40. A. Nicholls, B. Honig, J. Comp. Chem. 12, 435 (1991).
41. Used with kind permission of M. E. M. Noble, unpublished.
42. S. V. Evans, J. Mol. Graph. 11, 134 (1993).
43. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr, V, Val; W, Trp; and Y, Tyr,
44. This article is dedicated to the beloved memory of Cesar Milstein. We are grateful to T. Waks, Z. Eshhar, and A. Bloomer for their support; to P. Evans, G. Evans, A. Leslie, E. Blanc, and G. Bricogne for help and advice with data collection and structure determination; and to I. Wilson for constructive criticism. Supported by a Wellcome Trust grant.