A model of fibrin formation based on crystal structures of fibrinogen and fibrin fragments complexed with synthetic peptides

AUTOR(ES)

Yang, Zhe

FONTE

The National Academy of Sciences

RESUMO

A blood clot is a meshwork of fibrin fibers built up by the systematic assembly of fibrinogen molecules proteolyzed by thrombin. Here, we describe a model of how the assembly process occurs. Five kinds of interaction are explicitly defined, including two different knob–hole interactions, an end-to-end association between γ-chains, a lateral association between γ-chains, and a hypothetical lateral interaction between β-chains. The last two of these interactions are responsible for protofibril association and are predicated on intermolecular packing arrangements observed in crystal structures of fibrin double-D fragments cocrystallized with synthetic peptides corresponding to the knobs exposed by the release of the fibrinopeptides A and B.

Documentos Relacionados

• Fibrinogen and fibrin structure and fibrin formation measured by using magnetic orientation.
• Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.
• Discrimination between fibrin and fibrinogen by a monoclonal antibody against a synthetic peptide.
• Synthetic peptide derivatives that bind to fibrinogen and prevent the polymerization of fibrin monomers
• Synthetic peptide derivatives that bind to fibrinogen and prevent the polymerization of fibrin monomers