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Atomic Structural Models of Fibrin Oligomers
Artem Zhmurov1, Anna D Protopopova2, Rustem I Litvinov3
1Moscow Institute of Physics & Technology, Dolgoprudny, Moscow Region 141700, Russian Federation; Sechenov University, Moscow 119991, Russian Federation.
Structure (London, England : 1993)
|May 15, 2018
Summary
Researchers created atomic models of fibrin protofibrils, essential for blood clots. This breakthrough reveals key structural details, advancing our understanding of fibrin polymerization and clot formation.
Area of Science:
- Biophysics
- Biochemistry
- Structural Biology
Background:
- Fibrinogen self-assembles into fibrin protofibrils, forming the branched network crucial for blood clots and thrombi.
- Understanding fibrin structure is key to comprehending hemostasis and thrombosis.
Purpose of the Study:
- To reconstruct complete atomic models of double-stranded fibrin protofibrils.
- To elucidate the roles of specific structural features like crosslinking and knob-hole bonds in fibrin assembly.
- To provide atomic-level insights into the early stages of fibrin polymerization.
Main Methods:
- Multiscale modeling in silico combined with atomic force microscopy (AFM) imaging.
- Reconstruction and validation of atomic models against experimental AFM data.
- Characterization of protofibril mechanical properties and hydrodynamic parameters.
Main Results:
- Complete atomic models of double-stranded fibrin protofibrils, including γ-γ crosslinking, A:a and B:b knob-hole bonds, and αC regions, were successfully generated.
- Models were validated against high-resolution AFM images of fibrin oligomers and protofibrils up to 19 monomers.
- Protofibril twisting, bending, kinking, and A:a bond reversibility were characterized.
Conclusions:
- Atomic structures of fibrin protofibrils offer unprecedented detail on early fibrin polymerization.
- These findings provide a foundation for understanding the molecular mechanisms governing clot formation.
- The study bridges in silico modeling and experimental imaging to reveal complex biomolecular structures.
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