A model of fibrin formation based on crystal structures of fibrinogen and fibrin fragments complexed with synthetic peptides.
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 gamma-chains, a lateral association between gamma-chains, and a hypothetical lateral interaction between beta-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.
Yang
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Z
Center for Molecular Genetics, University of California at San Diego, La Jolla, CA 92093-0634, USA.
Mochalkin
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I
Doolittle
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RF
D003198:Computer Simulation; D003460:Crystallization; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*
D010446:Peptide Fragments; D005337:Fibrin; D005340:Fibrinogen