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 fragments1-8, 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 fragment1 of the anti-hen egg-white lysozyme (HEL) monoclonal antibody D1.3 (ref. 9), 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 Å for VH (aligning on VL) or of 0.5 Å for VL (aligning on VH). This is indicative of an induced fit rather than a 'lock and key' fit to the antigen. © 1990 Nature Publishing Group.