Structural Basis of Interfacial Flexibility in Fibrin Oligomers

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. [Display omitted] •Atomic models for single- and double-stranded fibrin oligomer are reconstructed•Structures are validated by quantitative comparison with high-resolution AFM images•Structural basis for interfacial flexibility of fibrin oligomers is provided•Atomic structure of the D:E:D interface beyond the knob-hole bonds is characterized Using the crystal structures of fibrin(ogen) and its fragments and advanced molecular modeling techniques, Zhmurov et al. recreate the full-atomic structures of single- and double-stranded fibrin oligomers and identify a hinge-like inter-monomer juncture region. These structures are validated by quantitative comparisons with high-resolution atomic force microscopy images.