Fibrinogen hydrophobicity plots

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. 

Trbased Hydrophobicity Plots of Human Fibrinogen Chains... 

Figure 7.29. Single residue (A) and mean residue (B) hydrophobicity plots of human y-fibrinogen. The most striking feature of the mean residue plot is the hydrophobic sequence, residues 337 to 379, experimentally shown to provide the Ea site for interaction with the a-chain amino-terminus on removal of the A peptide and exposure of GPRP and its surrounding hydrophobic residues for association with the hydrophobic domain of the Ea site shown in Figure...

The mean residue hydrophobicity plot of BP-fibrinogen in Figure 7.30B exhibits two minor hydrophobic sequences near residues 115 and 375 that could serve hydrophobic folding and assembly within the fibrinogen molecule, but would be less likely to participate in the hydrophobic association between molecules. 

Accordingly, by simple inspection of the mean hydrophobicity plot for y-fibrinogen, we see the activation of fibrinogen as the emergence of a site for hydrophobic association with the most hydrophobic sequence in a second molecule. 

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