Fibrinogen Kurashiki (γ G268E) Fibrin Network Structure

Abstract

<jats:p>Upon thrombin-catalyzed proteolytic conversion of fibrinogen to fibrin, fibrinopeptide A release exposes an N-terminal polymerization site (‘E<jats:sub>A</jats:sub>’) in the central E domain that interacts with a constitutive complementary site in each outer D domain (‘D<jats:sub>a</jats:sub>’) to drive the molecular assembly process by end-to-middle domain non-covalent ‘D<jats:sub>a</jats:sub>:E<jats:sub>A</jats:sub>’ interactions. End-to-end aligned doublestranded fibrils are formed in coordination with another recently described constitutive self-association site (termed ‘D:D’)that is situated at the outer end of each D domain. The D:D site contributes to end-to-end molecular alignment of fibrin molecules within each fibril strand. Concomitant branching and lateral fibril associations to form thick fibers, lead to formation of the mature fibrin clot.</jats:p><jats:p>Fibrinogen ‘Kurashiki’ is a unique congenital dysfibrinogenemia that was identified in a homozygous father and his heterozygous son. The abnormality involves a γ chain amino acid mutation (γ G268E) and is characterized by delayed and abnormal fibrin polymerization.</jats:p>