The crystal structure of modified bovine fibrinogen

Here we report the crystal structure at approximate to 4-Angstrom resolutio n of a selectively proteolyzed bovine fibrinogen. This key component in hem ostasis is an elongated 340-kDa glycoprotein in the plasma that upon activa tion by thrombin self-assembles to form the fibrin clot. The crystals are u nusual because they are made up of end-to-end bonded molecules that form fl exible filaments. We have visualized the entire coiled-coil region of the m olecule, which has a planar sigmoidal shape, The primary polymerization rec eptor pockets at the ends of the molecule face the same way throughout the end-to-end bonded filaments, and based on this conformation, we have develo ped an improved model of the two-stranded protofibril that is the basic bui lding block in fibrin. Near the middle of the coiled-coil region, the plasm in-sensitive segment is a hinge about which the molecule adopts different c onformations. This segment also includes the boundary between the three- an d four-stranded portions of the coiled coil, indicating the location on the backbone that anchors the extended flexible A alpha arm. We suggest that a flexible branch point in the molecule may help accommodate variability in the structure of the fibrin clot.