Three-dimensional structure of an antigen–antibody complex at 6 Å resolution (original) (raw)

Nature volume 313, pages 156–158 (1985)Cite this article

Abstract

Present understanding of the three-dimensional structure of antibody combining sites is based on X-ray diffraction studies of myeloma immunoglobulins (reviewed in refs 1, 2). The structures of the antigen-binding fragment (Fab) complexes of two of these immunoglobulins with small ligands have also been determined3,4. However, there is no crystallographic information concerning the interactions of an antibody with an antigen, nor do we know the precise structure of antigenic determinants on protein molecules (reviewed in ref. 5). We now report the first structure determination of an antigen–antibody complex at 6 Å resolution. The structure of the complex between hen egg-white lysozyme and the Fab of a monoclonal anti-lysozyme antibody (D1.3) shows that the combining site of antibodies is not merely a cleft delineated by the complementarity-determining regions of the variable regions of the light and heavy chains, but is a larger area extending beyond it. A correspondingly large area of the antigen makes close contacts with the antibody, in agreement with the notion of a ‘topographical’ rather than ‘sequential’ antigenic determinant. The structural basis of cross-reactivities of an antibody with heterologous antigens and the effect of a single amino acid substitution on antigenic specificity can thus be visualized in the structural model presented here.

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Authors and Affiliations

  1. Département d'Immunologie, Institut Pasteur, 75724, Paris, Cedex 15, France
    A. G. Amit, R. A. Mariuzza, S. E. V. Phillips & R. J. Poljak

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  1. A. G. Amit
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  2. R. A. Mariuzza
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  3. S. E. V. Phillips
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  4. R. J. Poljak
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Amit, A., Mariuzza, R., Phillips, S. et al. Three-dimensional structure of an antigen–antibody complex at 6 Å resolution.Nature 313, 156–158 (1985). https://doi.org/10.1038/313156a0

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