Fibrinogen and Fibrin

Abstract

Fibrinogen is a soluble plasma protein that is converted to polymeric fibrin in response to damage to the vascular system. The clotting process is initiated when platelets aggregate at the wound site. Their disruption releases biologically active amines and a proteolytic cascade follows which culminates in the conversion of fibrinogen to fibrin. The fibrin polymer forms the matrix of the tangle of cellular and molecular substances called the blood clot. Atomic‐level details are now in hand for many of the interactions that hold fibrin units together, although some aspects have yet to be resolved. Of necessity, fibrin clots need to be dismantled when they are no longer needed, an operation largely accomplished by the proteolytic enzyme plasmin. Various regulatory phenomena are involved in maintaining the balance between intravascular fluidity and clots that prevent blood loss. A variety of hereditary conditions, including mutant fibrinogens, can predispose individuals to either thrombosis or bleeding.

Key concepts:

  • The underlying fabric of blood clots is a protein polymer called fibrin.

  • Fibrin clots are formed in response to injuries to any part of the vascular system.

  • The conversion of soluble fibrinogen molecules to insoluble fibrin depends on thrombin generated from prothrombin.

Keywords: fibrinogen; fibrin; clot stabilisation; fibrinolysis; blood clotting; X‐ray structures

Figure 1.

Schematic structure of fibrinogen showing its dimeric nature with three different polypeptide chains proceeding away from a central dyad. The exact whereabouts of the α chain carboxyl domains are still uncertain.

Figure 2.

Ribbon representation of fibrinogen showing the coiled coils and globular β and γ carboxyl domains. Colour scheme: green, α chain; magenta, β chain; cyan, γ chain. γC and βC denote the C‐terminal domains of γ and β chains, respectively; GPRP is the A knob and GHRP is the B knob; Ca, calcium binding sites; CH2O, carbohydrate clusters. Reproduced from Yang et al.. Reprinted with permission from American Chemical Society.

Figure 3.

Ribbon representation of parts of three fibrinogen molecules showing how the A and B knobs from the central region of one molecule (bottom) bind to the terminal regions of two other fibrinogens to form fibrin. The broken lines correspond to putative connections and have not been observed directly in X‐ray structures. Colour scheme: blue, α chain; red, β chain; green, γ chain; XL=γ–γ crosslink formed by factor XIII. Adapted from Yang et al..

Figure 4.

Three views of two‐molecule‐thick protofibril showing half‐molecule overlap. kh=region of knob–hole interactions. Colour scheme: cyan, α chain; magenta, β chain; green, γ chain. Reproduced from Yang et al..

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Further Reading

Doolittle RF (2003) Structural Basis of the fibrinogen–fibrin transformation: contributions from X‐ray crystallography. Blood Reviews 17: 33–41.

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How to Cite close
Doolittle, Russell F(Jun 2010) Fibrinogen and Fibrin. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001409.pub2]