Structure of an anti-idiotypic Fab against feline peritonitis virus-neutralizing antibody and a comparison with the complexed Fab.
The crystal structure of anti-idiotopic Fab 409.5.3, made against an E2 specific feline infectious peritonitis virus-neutralizing antibody 730.1.4, has been determined in its free from, at 2.9 A resolution by molecular replacement. This antibody, used as an immmunogen, elicits the production of anti-anti-idiotypic antibodies that in turn neutralize the virus. The structure of the uncomplexed Fab was refined using constrained-restrained least squares minimization and simulated annealing in combination with conjugate gradient techniques to a crystallographic R of 0.22 based on 16,482 unique reflections between 20.0 and 2.9 A. The free antiidiotypic Fab shows, when compared to its complexed form, a 5 degrees rotation of its variable light with respect to its variable heavy domain and rearrangement of complementarity determining region loops, which permits optimization of the stereocomplementarity between interacting molecules. This finding supports the induced fit hypothesis for antibody antigen interaction.
Ban
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Department of Biochemistry, University of California, Riverside 92521.
Escobar
C
C
Hasel
K W
KW
Day
J
J
Greenwood
A
A
McPherson
A
A
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry* / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology*; D016765:Coronavirus, Feline / Q000276:immunology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
D000888:Antibodies, Anti-Idiotypic; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region