Conformational change in an anti-integrin antibody: structure of OPG2 Fab bound to a beta 3 peptide

Antibodies are important tools to explore receptor-ligand interactions. The anti-integrin antibody OPG2 binds in an RGD-related manner to the alphaIIb beta3 integrin as a molecular mimic of fibrinogen. The Fab fragment from OPG2 was cocrystallized with a peptide from the beta3 subunit of the integri...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-10, Vol.251 (1), p.61-66
Main Authors: Kodandapani, R, Veerapandian, L, Ni, C Z, Chiou, C K, Whittal, R M, Kunicki, T J, Ely, K R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antigen-Antibody Complex - chemistry
Antigen-Antibody Complex - metabolism
Binding Sites, Antibody
Crystallization
Immunoglobulin Fab Fragments - chemistry
Immunoglobulin Fab Fragments - metabolism
Models, Molecular
Molecular Sequence Data
Oligopeptides - metabolism
Platelet Glycoprotein GPIIb-IIIa Complex - chemistry
Platelet Glycoprotein GPIIb-IIIa Complex - immunology
Platelet Glycoprotein GPIIb-IIIa Complex - metabolism
Protein Conformation
Solutions
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Summary:Antibodies are important tools to explore receptor-ligand interactions. The anti-integrin antibody OPG2 binds in an RGD-related manner to the alphaIIb beta3 integrin as a molecular mimic of fibrinogen. The Fab fragment from OPG2 was cocrystallized with a peptide from the beta3 subunit of the integrin representing a site that binds RGD. The crystal structure of the complex was determined at 2.2-A resolution and compared with the unbound Fab. On binding the integrin peptide there were conformational changes in CDR3 of the heavy chain. Also, a significant shift across the intermolecular interface between the CH1-CL domains was observed so that the angle of rotation relating the two domains was reduced by 15 degrees. This unusual conformational adjustment represents the first example of ligand-induced conformational changes in the carboxyl domains of a Fab fragment.
ISSN:0006-291X
DOI:10.1006/bbrc.1998.9380