Fibrin polymers

Fibrinogen --< F brht-rnonomer Fibrin-polymer The agregates... 

Fibrin polymers are responsible for the fibrin-dependent enhancement of Factor XIII activation (Greenberg et al, 2003). The mechanism for this effect involves the formation of a tight ternary complex between fibrin, Factor XIII, and thrombin, accompanied by a conformational change of Factor XIII that exposes the active site, after which Factor XHIa remains bound to fibrin. However, the B chains dissociate, which is necessary to expose the active site cysteine of plasma Factor XIII. Platelet Factor XIII without the B chains, is more rapidly activated by thrombin than plasma Factor XIII because of the time that it takes for the B chains to dissociate. 

Galanakis, D. K., Lane, B. P., and Simon, S. R. (1987). Albumin modulates lateral assembly of fibrin polymers Evidence of enhanced fine fibril formation and of unique synergism with fibrinogen. Biochem. 26, 2389-2400. 

Mosesson, M. W., DiOrio, J. P., Siebenlist, K. R., Wall, J. S., and Hainfeld, J. F. (1993). Evidence for a second type of fibril branch point in fibrin polymer networks, the trimolecular junction. Blood 82, 1517-1521. 

Finally, the common pathway involves thrombin in a number of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a haemostatic plug. In addition, it activates factors VIII and V and their inhibitor protein C (in the presence of thrombomoduhn), and it activates factor XIII, which cross-links the fibrin polymers. 

Envenomation from a crotalid bite leaves one or more puncture wounds with a potential for progressive edema and ecchymosis. Crotalid venom contains a mixture of proteins, lipids, and metals. The venom forms fibrin polymers, which are susceptible to normal fibrinolysis and phagocytosis. It is represented by falling fibrinogen levels. Copperhead venom has a weak effect on this series of events in coagulation, resulting in lower morbidity after envenomation. 

The overwhelming majority of peptide bonds in proteins occur between a-amino and a-carboxylate groups, giving a single linear unbranched chain. In rare, but important, cases, side-chain amino and carboxylate groups can be joined by an isopeptide bond to create a branch (as in joining the C-terminus of the small protein ubiquitin to another protein) or to provide cross links (as in fibrin polymers in a blood clot). 

New hybrids of plasminogen activator have been constructed in attempts to increase the specificity toward fibrin polymers and thereby improve the therapeutic value for treatment of coronary artery thrombosis (143, 144). Plasminogen activators are serine proteases that act on plasminogen to release plasmin, also a... 

Brown AEX, Litvinov RI, Discher DE et al (2009) Multiscale mechanics of fibrin polymer gel stretching with protein unfolding and loss of water. Science 325 741-744... 

A and B, and to produce a fibrin monomer. The new N-termini of the a and 3 chains now bind to the terminal domain of a different fibrin monomer causing the spontaneous polymerization to form insoluble fibrin polymers. This fibrin network is further strengthened by the introduction of covalent cross-links by factor Xllla. 

The clot thus formed is stiU not completely stable and will come apart if not covalently cross-linked. As discussed above, thrombin acts on fibrinogen and clips off fibrinopeptides to form the fibrin monomer. The fibrin monomer molecules come close to each other to form a loose fibrin polymer. Thrombin then activates factor XIII to Xllla which stabilizes the clot by forming amide bonds between the fibrin polymer chains (stabilization phase). 

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