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 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.
Kodandapani
R
R
Cancer Research Center, The Burnham Institute, La Jolla, California, 92037, USA.
Veerapandian
L
L
Ni
C Z
CZ
Chiou
C K
CK
Whittal
R M
RM
Kunicki
T J
TJ
Ely
K R
KR
D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000378:metabolism; D001666:Binding Sites, Antibody; D003460:Crystallization; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation; D012996:Solutions
D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012996:Solutions; C047981:arginyl-glycyl-aspartic acid