Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 97, Issue 26, Pages 14156-14161Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.26.14156
Keywords
blood clots; crystal packing; protofibrils; macromolecular assembly
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Funding
- NHLBI NIH HHS [R01 HL026873, HL26873] Funding Source: Medline
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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.
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