Figure 4.
PT25-2 Fab binding prevents the αIIbβ3 ectodomain from adopting the fully bent-closed conformation. (A) Two perpendicular views of a hybrid atomic model of the PT25-2 Fab bound to the αIIbβ3 headpiece are shown. The PT25-2 Fab causes steric clashes with the αIIb leg and prevents the interaction of the β3 lower leg with the β3 hybrid domain that stabilizes the fully bent-closed conformation. (B) View of the hybrid atomic model of the PT25-2 Fab-bound αIIbβ3 headpiece showing the arrangement of the domains in the lower legs. Binding of the PT25-2 Fab to the αIIb β propeller displaces the αIIb calf-1 and calf-2 domains, which thus no longer stabilize the position of the β3 lower leg domains and, in turn, no longer support the interaction of the EGF-3 and EGF-4 domains with the hybrid domain, the main interactions stabilizing the fully bent-closed conformation.

PT25-2 Fab binding prevents the αIIbβ3 ectodomain from adopting the fully bent-closed conformation. (A) Two perpendicular views of a hybrid atomic model of the PT25-2 Fab bound to the αIIbβ3 headpiece are shown. The PT25-2 Fab causes steric clashes with the αIIb leg and prevents the interaction of the β3 lower leg with the β3 hybrid domain that stabilizes the fully bent-closed conformation. (B) View of the hybrid atomic model of the PT25-2 Fab-bound αIIbβ3 headpiece showing the arrangement of the domains in the lower legs. Binding of the PT25-2 Fab to the αIIb β propeller displaces the αIIb calf-1 and calf-2 domains, which thus no longer stabilize the position of the β3 lower leg domains and, in turn, no longer support the interaction of the EGF-3 and EGF-4 domains with the hybrid domain, the main interactions stabilizing the fully bent-closed conformation.

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