title: The crystal structure of modified bovine fibrinogen.
abstract: Here we report the crystal structure at approximately 4-A resolution of a selectively proteolyzed bovine fibrinogen. This key component in hemostasis is an elongated 340-kDa glycoprotein in the plasma that upon activation by thrombin self-assembles to form the fibrin clot. The crystals are unusual because they are made up of end-to-end bonded molecules that form flexible filaments. We have visualized the entire coiled-coil region of the molecule, which has a planar sigmoidal shape. The primary polymerization receptor 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 developed an improved model of the two-stranded protofibril that is the basic building block in fibrin. Near the middle of the coiled-coil region, the plasmin-sensitive segment is a hinge about which the molecule adopts different conformations. This segment also includes the boundary between the three- and four-stranded portions of the coiled coil, indicating the location on the backbone that anchors the extended flexible Aalpha arm. We suggest that a flexible branch point in the molecule may help accommodate variability in the structure of the fibrin clot.
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Volkmann
authors.forename: G
authors.initials: G
authors.lastname: Jun
authors.forename: A H
authors.initials: AH
authors.lastname: Henschen-Edman
authors.forename: C
authors.initials: C
authors.lastname: Cohen
mesh_terms: D000818:Animals; D002417:Cattle; D003460:Crystallization; D018360:Crystallography, X-Ray; D010450:Endopeptidases; D005340:Fibrinogen / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D005340:Fibrinogen; D010450:Endopeptidases