Fibrinogen is composed of three pairs of polypeptide chains, termed Aα, Bβ and γ, respectively. Proteolytic conversion of fibrinogen to fibrin by thrombin releases fibrinopeptide A and exposes an N-terminal polymerization site ('EA’) in the central E domain of the molecule. This site interacts with a constitutive complementary site in each outer D domain ('Da’) to drive the molecular assembly process by end-to-middle domain non-covalent ‘Da:EA’ interactions. End-to-end aligned double-stranded fibrils are formed in coordination with another recently described constitutive self-association site (termed ‘D:D’)fhat 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.
Fibrinogen Marburg is a homozygous hypodysfibrinogenemia lacking amino acid residues Aα461- 610 due to a stop codon at position 461 of the Aα chain.