Small rearrangements in structures of Fv and Fab fragments of antibody D1.3 on antigen binding

The potential use of monoclonal antibodies in immunological, chemical and clinical applications has stimulated the protein engineering and expression of Fv fragments, which are heterodimers consisting of the light and heavy chain variable domains (VL and VH) of antibodies. Although Fv fragments exhi...

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Bibliographic Details
Published in:Nature (London) 1990-10, Vol.347 (6292), p.483-485
Main Authors: BHAT, T. N, BENTLEY, G. A, FISCHMANN, T. O, BOULOT, G, POLJAK, R. J
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal
Antigen-antibody reactions, antigen-antibody complexes, antibody-complement and others. Study of affinity. Antigen presentation
Binding Sites, Antibody
Biological and medical sciences
Biology
Computer Graphics
Crystallography
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genetics
Immunoglobulin Fab Fragments - ultrastructure
Immunoglobulin Fragments - ultrastructure
In Vitro Techniques
Models, Molecular
Molecular immunology
Molecules
Muramidase - immunology
Protein Conformation
X-Ray Diffraction
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Summary:The potential use of monoclonal antibodies in immunological, chemical and clinical applications has stimulated the protein engineering and expression of Fv fragments, which are heterodimers consisting of the light and heavy chain variable domains (VL and VH) of antibodies. Although Fv fragments exhibit antigen binding specificity and association constants similar to their parent antibodies or Fab moieties, similarity in their interactions with antigen at the level of three-dimensional structure has not been investigated. We have determined the high-resolution crystal structure of the genetically engineered FvD1.3 fragment of the anti-hen egg-white lysozyme (HEL) monoclonal antibody D1.3, and of its complex with HEL. On comparison with the crystallographically refined FabD1.3-HEL complex, we find that FvD1.3 and FabD1.3 make, with minor exceptions, very similar contacts with the antigen. Furthermore, a small but systematic rearrangement of the domains of FvD1.3 occurs on binding HEL, bringing the contacting residues closer to the antigen by a mean value of about 0.7 A for VH (aligning on VL) or of 0.5 A for VL (aligning on VH). This is indicative of an induced fit rather than a 'lock and key' fit to the antigen.
ISSN:0028-0836
1476-4687
DOI:10.1038/347483a0