title: Crystal structure of the central region of bovine fibrinogen (E5 fragment) at 1.4-A resolution.
abstract: The high-resolution crystal structure of the N-terminal central region of bovine fibrinogen (a 35-kDa E(5) fragment) reveals a remarkable dimeric design. The two halves of the molecule bond together at the center in an extensive molecular "handshake" by using both disulfide linkages and noncovalent contacts. On one face of the fragment, the Aalpha and Bbeta chains from the two monomers form a funnel-shaped domain with an unusual hydrophobic cavity; here, on each of the two outer sides there appears to be a binding site for thrombin. On the opposite face, the N-terminal gamma chains fold into a separate domain. Despite the chemical identity of the two halves of fibrinogen, an unusual pair of adjacent disulfide bonds locally constrain the two gamma chains to adopt different conformations. The striking asymmetry of this domain may promote the known supercoiling of the protofibrils in fibrin. This information on the detailed topology of the E(5) fragment permits the construction of a more detailed model than previously possible for the critical trimolecular junction of the protofibril in fibrin.
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA.
authors.forename: J
authors.initials: J
authors.lastname: Madrazo
authors.forename: J H
authors.initials: JH
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Litvinovich
authors.forename: R
authors.initials: R
authors.lastname: Dominguez
authors.forename: S
authors.initials: S
authors.lastname: Yakovlev
authors.forename: L
authors.initials: L
authors.lastname: Medved
authors.forename: C
authors.initials: C
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D019281:Dimerization; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C018543:fibrinogen fragment E; D005340:Fibrinogen