Conformational changes in fibrinogen elicited by its interaction with platelet membrane glycoprotein GPIIb-IIIa.
The binding of fibrinogen to membrane glycoprotein GPIIb-IIIa on activated platelets leads to platelet aggregation. This interaction results in conformational changes in fibrinogen as evidenced by the expression of receptor-induced binding sites, RIBS, epitopes which are expressed by the bound but not the free ligand. In the present study, two RIBS epitopes have been localized. One sequence resides at gamma 112-119 and is recognized by mAb 9F9; the second is the RGDF sequence at A alpha 95-98 and is recognized by mAb 155B16. These epitopes are also exposed by adsorption of fibrinogen onto a plastic surface and digestion of the molecule by plasmin. Proteolytic exposure of the epitopes coincides with cleavage of the carboxyl-terminal aspects of the A alpha-chains to form fragment X2. The inaccessibility of the RGDF sequence at A alpha 95-98 in fibrinogen suggests that this sequence does not participate in the initial binding of the molecule to GPIIb-IIIa. The location of these RIBS epitopes suggests a model in which binding of fibrinogen to its receptor alters the conformation of the carboxyl-terminal aspects of the A alpha-chains, exposing the sequences which reside in the coiled-coil connector segments between the D and E domains of the molecule. These sequences may then serve as epitopes and may mediate unique functions of the receptor-bound molecule.
Ugarova
T P
TP
Committee on Vascular Biology, Scripps Research Institute, La Jolla, California 92037.
Budzynski
A Z
AZ
Shattil
S J
SJ
Ruggeri
Z M
ZM
Ginsberg
M H
MH
Plow
E F
EF
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005340:Fibrinogen / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011487:Protein Conformation
D000939:Epitopes; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D005341:Fibrinolysin