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Figure 4.
Fig. 4. Schematic diagram of thrombin and GpIb-IX complexes, in
which GpIb  and thrombin
molecules are arranged as an adhesive ribbon structure observed
in the crystals (color coding is the same as in Figs. 1, 2, 3).
The region between the last residue observed in GpIb (sTyr279) and the
stalk region is shown as green dotted lines. GpIb is
covalently attached to GpIbß by means of a disulfide bond
near the extracellular surface of the membrane, and GpIb-IX-V is
present as a noncovalent 2:2:1 complex on the platelet surface
(1, 16). GpV is not included in the model, because recent
evidence suggests that the extracellular domain of GpV (removed
from the receptor complex by thrombin cleavage early in the
aggregation process) functions as an inhibitor of platelet
activation and aggregation (14). The model is further simplified
as a 1:1 GpIb-IX complex. The orientation of multiple complexes
with respect to membranes is deduced from the location of the
C-terminal end of the GpIb fragment relative
to the thrombin-binding domains. Simultaneous binding of two
GpIb receptors at two
polar ends of the bridging thrombin molecule stabilizes
antiparallel orientations of adjacent receptors and ensures that
these neighboring receptors extend their C-terminal ends in
opposite directions. The long axis of each GpIb receptor is
oriented roughly normal to the platelet membrane, with the
C-terminal end positioned toward the membrane and extending away
from sites of thrombin attachment. A long O-glycosylated
mucin-like stalk (not drawn to scale) of the GpIb receptor places
its thrombin binding domain  45 nm away from the
platelet membrane surface (39); thus, platelet membranes that
are about 100 nm apart could be linked together by binding
interactions between GpIb and thrombin.
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