Structural Basis of Interfacial Flexibility in Fibrin Oligomers

Structure. 2016 Nov 1;24(11):1907-1917. doi: 10.1016/j.str.2016.08.009. Epub 2016 Sep 29.


Fibrin is a filamentous network made in blood to stem bleeding; it forms when fibrinogen is converted into fibrin monomers that self-associate into oligomers and then to polymers. To gather structural insights into fibrin formation and properties, we combined high-resolution atomic force microscopy of fibrin(ogen) oligomers and molecular modeling of crystal structures of fibrin(ogen) and its fragments. We provided a structural basis for the intermolecular flexibility of single-stranded fibrin(ogen) oligomers and identified a hinge region at the D:D inter-monomer junction. Following computational reconstruction of the missing portions, we recreated the full-atomic structure of double-stranded fibrin oligomers that was validated by quantitative comparison with the experimental images. We characterized previously unknown intermolecular binding contacts at the D:D and D:E:D interfaces, which drive oligomerization and reinforce the intra- and inter-strand connections in fibrin besides the known knob-hole bonds. The atomic models provide valuable insights into the submolecular mechanisms of fibrin polymerization.

Keywords: D:D interface; D:E:D interface; MD simulations on a GPU; fibrin; fibrin oligomers; fibrin polymerization; fibrinogen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Fibrin / chemistry*
  • Fibrinogen / chemistry*
  • Humans
  • Microscopy, Atomic Force
  • Models, Molecular
  • Polymerization
  • Protein Conformation


  • Fibrin
  • Fibrinogen