Fibrinogen subunit structure

The crystal structure of approximately 70% of the residues of chicken fibrinogen has become available from the laboratory of Doolittle and coworkers as shown in Figure 7.27B. The (Aa)2(BP)2(y)2 subunit structure combines to form a flattened sigmoidal or S-like shape, which with the missing sequences will be indicated as (aPya PY)-The amino termini of all six chains, the two chains—aa, PP, and y/—all meet in the central part of the structure. 

Mckee, A. Mattock, R HUl, R. L. Subunit Structure of Human Fibrinogen, Soluble Fibrin and Cross-Linked Insoluble Fibrin. Proc. Natl. Acad. USA, 1970,66,738. 

Comparative sequence analysis of even well described inter-protein interactions (i.e., from X-ray structure of multi-domain or subunit proteins) has only recently been possible initial results have however shown some common features of quaternary interactions. There is hope that interactions in naturally selfassociating proteins will be similar to those that lead to irreversible interactions in refolded proteins, and that one can then use this knowledge to prevent precipitation. For example, fibrin clots can be dissolved by adding the tetra-peptide Gly-Pro-Arg-Pro, the amino acids at the N-termini of fibrinogen molecules after thrombin cleavage. A related peptide, Arg-Gly-Asp-Ser, from the carboxy- terminus of fibrinogen, inhibits platelet aggregation. ... 

Formation of a blood clot involves a complex cascade of enzymatically controlled reactions the penultimate step of which is the formation of thrombin. Thrombin then cleaves peptides from fibrinogen to form fibrin monomers that associate to form the fibrin clot. Fibrin clot formation is a carefully poised process whereby a relatively minor injury will not allow excessive bleeding and result in death and whereby excessive clot formation will not block blood flow and result in death. As will be seen by examination of the relevant molecular structures, regardless of the balance struck, the key process of clot formation is the hydrophobic association of fibrin monomers. In demonstrating this perspective, the same T,-based mean residue hydrophobicity plot will be used as was used above in Figure 7.9 for understanding the hydrophobic association of hemoglobin subunits. 

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