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Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy
Ist Teil von
The Journal of biological chemistry, 1992-08, Vol.267 (23), p.16637-16643
Ort / Verlag
United States: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1992
Quelle
MEDLINE
Beschreibungen/Notizen
The platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa), is a calcium-dependent heterodimer that binds fibrinogen, von Willebrand
factor, and fibronectin after platelet activation. We examined GPIIb-IIIa alone and bound to these ligands by electron microscopy
after rotary shadowing with platinum/tungsten. We found, as observed previously, that in the presence of detergent and 2 mM
Ca2+, GPIIb-IIIa consists of an 8 x 12-nm globular head with two 18-nm flexible tails extending from one side. We also found
that in the presence of EDTA, GPIIb-IIIa dissociates into two similar comma-shaped subunits, each containing a portion of
the globular head and a single tail. Using monoclonal antibodies to GPIIb, GPIIIa, and the GPIIb-IIIa heterodimer, we found
that the tails contained the carboxyl termini of each subunit, while the nodular head was composed of amino-terminal segments
of both subunits. Electron microscopy of GPIIb-IIIa bound to fibrinogen revealed a highly specific interaction of the nodular
head of GPIIb-IIIa with the distal end of the trinodular fibrinogen molecule and with the tails of GPIIb-IIIa extended laterally
at an angle of approximately 98 degrees with respect to the long axis of fibrinogen. When a GPIIb-IIIa was bound to each end
of a single fibrinogen, the tails were oriented to opposite sides of fibrinogen, enabling fibrinogen to bridge two adjacent
platelets. Electron microscopy of GPIIb-IIIa bound to fibronectin revealed GPIIb/IIIa-binding sites approximately two-thirds
of the distance from the amino terminus of each end of the fibronectin molecule, while GPIIb-IIIa was found to bind to von
Willebrand factor protomers along a rod-like region near the central nodule of the molecule.