Fibrinogen and fibrin structure and functions

  title={Fibrinogen and fibrin structure and functions},
  author={Michael W. Mosesson},
  journal={Journal of Thrombosis and Haemostasis},
  • M. Mosesson
  • Published 1 August 2005
  • Biology
  • Journal of Thrombosis and Haemostasis
Summary.  Fibrinogen molecules are comprised of two sets of disulfide‐bridged Aα‐, Bβ‐, and γ‐chains. Each molecule contains two outer D domains connected to a central E domain by a coiled‐coil segment. Fibrin is formed after thrombin cleavage of fibrinopeptide A (FPA) from fibrinogen Aα‐chains, thus initiating fibrin polymerization. Double‐stranded fibrils form through end‐to‐middle domain (D:E) associations, and concomitant lateral fibril associations and branching create a clot network… 

Structure and Functions of Fibrinogen and Fibrin

Fibrinogen molecules consist of three pairs of disulfide-bridged chains joined together in the amino-terminal central E domain, which is connected by coiled coils to its outer D domains to account for the complete elastic recovery of maximally stretched fibrin after maximum clot deformation.

The structure of soluble fibrin oligomers

This work has shown that, in the presence of mod erate concentrations of urea, the formation of equili brated soluble rod shaped oligomers was observed both in the case of desAABB fibrin and desAAfibrin, derived from fibr inogen, respectively, under the treat ment with either thrombin or reptilase.

Disturbance of functional properties of fibrinogen under ozone oxidation

Fibrinogen is a soluble plasma protein that plays the key role in fibrinogenesis. This is a dimer consisting of three pairs of polypeptide chains ( A α , B β , γ ) 2 , which form five major domains:

Fibrinogen and factor XIII at the intersection of coagulation, fibrinolysis and inflammation.

  • B. Hoppe
  • Biology, Medicine
    Thrombosis and haemostasis
  • 2014
The present review summarises current knowledge of fibrinogen's and factor XIII's function in coagulation and fibrinolysis giving special emphasis on their relation to inflammation control.

Roles of fibrin α- and γ-chain specific cross-linking by FXIIIa in fibrin structure and function.

It is shown that α- and γ-chain cross-linking play independent and specific roles in fibrin clot formation and structure.

Chorography and conformational dynamism of the Soluble Human Fibrinogen in solution

This work provides a molecular basis for the structural “dynamism” of fibrinogen that is expected to influence the broad swath of functionally diverse macromolecular interactions and fine-tune the structural and mechanical properties of blood clots.

Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling

The structural models of the fibrinogen α-chain (excluding two highly flexible regions) and the N termini of the β-chain are constructed, confirm these models with known structural arrangements, and map how the structure laterally aggregates to form intricate lattices together with the γ-chain.

Flexible regions in the molecular architecture of Human fibrin clots structurally resolved by XL-MS and integrative structural modeling

The resulting model will be invaluable for research on dysfibrinogenemia and amyloidosis, as it provides insights into the molecular mechanisms of thrombosis and bleeding disorders related to fibr inogen variants.

Altered structure and function of fibrinogen after cleavage by Factor VII Activating Protease (FSAP).

Phase Separation of Intrinsically Disordered Protein Polymers Mechanically Stiffens Fibrin Clots

The ability of protein‐based phase separation to modulate the physical and biochemical properties of blood clots is demonstrated and protein phase separation is suggested as a new mechanism for achieving hemostasis in clinical settings.



Cross‐linked γ‐chains in fibrin fibrils bridge transversely between strands: no

  • J. Weisel
  • Biology
    Journal of thrombosis and haemostasis : JTH
  • 2004
relevant data is summarized from X-ray crystallography, the products of lysis, electron microscopy, and studies of the interactions between fibrin and fibr inogen/fragment D to discuss the topology of these cross-links.

The covalent structure of factor XIIIa crosslinked fibrinogen fibrils.

Results indicate that carboxy terminal gamma chain bonds are positioned transversely between strands and are represented by thin filamentous structures bridging the D domains of opposing fibril strands--it follows that the same gamma chain crosslink arrangement occurs in fibrin.

Identification of covalently linked trimeric and tetrameric D domains in crosslinked fibrin.

Measurement of the widths of fibrils comprising trifunctional branches in thin fiber networks revealed tetramolecular branch points, which are formed by bifurcation of two double-stranded fibrilies.

Platelet‐Fibrinogen Interactions

  • J. Bennett
  • Biology
    Annals of the New York Academy of Sciences
  • 2001
Preliminary evidence suggests that it is the submembranous actin or actin‐associated proteins that constrains GPIIb‐IIIa in a low affinity state and that relief of this constraint by initiating actin filament turnover enables GP IIb‐ IIIa to bind fibrinogen.

Structure and Rheology of Fibrin Networks

This gel-like ‘fine’ clot formed from pure fibrinogen is remarkably close to perfectly elastic, obeying Hooke’s Law in small shearing deformations and having very little viscoelastic loss over many decades of time scale.

Fibrinogen assembly and crosslinking on a fibrin fragment E template.

These and other features of E-des A-based fibrinogen fibrils, including interstrand gamma chain bridges and early and extensive lateral fibril strand associations concomitant with accelerated gamma chain crosslinking, indicate thatCrosslinking of fibr in fibrill strands takes place preferentially on transversely positioned gamma chains.

Fibrin‐Mediated Plasminogen Activation

Molecular calculations and experimental data show that the site Aα148–160 in fibrinogen is covered among others by a part of the Aα chain that forms an α‐helix, and by a globular domain formed by the β‐chain, and it is conceivable that in the αC domain sites are involved in the early phases of fibrinolysis.

Crystal structure of a 30 kDa C-terminal fragment from the gamma chain of human fibrinogen.

The polymerization domain in the gamma chain is the most variable among a family of fibrinogen-related proteins and contains many acidic residues that contribute to the molecular dipole moment in the structure, which may allow electrostatic steering to guide the alignment offibrin monomers during the polymerization process.

Fibrinogen γ′ chain binds thrombin exosite II

Summary.  A high‐affinity thrombin‐binding site in an alternately processed fibrinogen variant, the γA/γ′ isoform, is characterized in this report. The binding site has been shown to be situated