       Document 0121
 DOCN  M94A0121
 TI    Major antigen-induced domain rearrangements in an antibody.
 DT    9412
 AU    Stanfield RL; Takimoto-Kamimura M; Rini JM; Profy AT; Wilson IA;
       Department of Molecular Biology, Scripps Research Institute, La; Jolla,
       CA 92037.
 SO    Structure. 1993 Oct 15;1(2):83-93. Unique Identifier : AIDSLINE
       MED/94348871
 AB    BACKGROUND: Recent structural results have shown that antibodies use an
       induced fit mechanism to recognize and bind their antigens. Here we
       present the crystallographically determined structure of an Fab directed
       against an HIV-1 peptide (Fab 50.1) in the unliganded state and compare
       it with the peptide-bound structure. We perform a detailed analysis of
       the components that contribute to enhanced antigen binding and
       recognition. RESULTS: Induced fit of Fab 50.1 to its peptide antigen
       involves a substantial rearrangement of the third complementarity
       determining region loop of the heavy chain (H3), as well as a large
       rotation of the variable heavy (VH) chain relative to the variable light
       (VL) chain. Analysis of other Fab structures suggests that the extent of
       the surface area buried at the VL-VH interface correlates with the
       ability to alter antibody quaternary structure by reorientation of the
       VL-VH domains. CONCLUSION: Fab 50.1 exhibits the largest conformational
       changes yet observed in a single antibody. These can be attributed to
       the flexibility of the variable region. Comparisons of new data with
       previous examples lend to the general conclusion that a small VL-VH
       interface, due in part to a short H3 loop, permits substantial
       alterations to the antigen-binding pocket. This has major implications
       for the prediction, engineering and design of antibody-combining sites.
 DE    Amino Acid Sequence  Comparative Study  Computer Graphics
       Crystallography, X-Ray/METHODS  HIV Antigens/*IMMUNOLOGY  HIV-1
       Immunoglobulins, Fab/*CHEMISTRY  Models, Molecular  Molecular Sequence
       Data  *Protein Conformation  *Protein Structure, Secondary  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Viral Proteins/*IMMUNOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

