Fibrin peptide sequences

Thus, the key process of fibrin clot formation is one of cleaving peptide sequences, the result of which is to lower the cusp of insolubility, representing the hydrophobic association between molecules, from above to below physiological temperature. 

Synthetic laminin-1 A10 and B160 peptide sequences were coupled to poly (L-lysine) coated glass or fibrin gels. In order to investigate a broad range of peptide surface concentrations in a single test specimen, a gradient in the peptide concentration on the polymer surfaces was prepared in one direction. The... 

The amino acid sequences of haptides comprise hydrophobic and cationic residues with a net charge of +4 to +5 per 19 to 21 amino acids. It was proposed that haptides could be attracted to the anionic liposomes as well as the anionic cell membrane and that the hydrophobic properties of the haptide facilitate membrane translocation (106). Haptide uptake was reported to be energy independent, occurring at 4°C. The advantage of this peptide compared to CPP such as TAT and Antp, is that, unlike the virus-derived peptides, the haptides are not recognized as foreign antigens and do not induce cell transformation (106). However, haptides have also been found to accelerate fibrin clot formation and lack cell specificity (106). 

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. ... 

Higher-resolution images reveal the detailed structure of the fibrin monomer, how the fibrin monomers come together, and how this assembly is facilitated by removal of the fibrinopeptides. The homologous (3 and y chains have globular domains at the carboxyl-terminal ends (Figure 10.40). These domains have binding holes that interact with peptides. The p domain is specific for sequences of the form HaN -Gly-His-Arg-, whereas the y domain binds HaN -Gly-Pro-Arg-. Exactly these sequences (some-... 

The amino acid sequences of the Aa (610 residues), BP (461 residues), and y (411 residues) chains of human fibrinogen are given in Table 7.1. ° Having the amino acid sequences directly available will be helpful in discussing the peptide cleavages and the interchain interactions relevant to fibrin formation. 

The absence of the residues noted does not appear to block an understanding of the key elements of fibrin formation as much as might have been initially expected. Binding of the key residue sequences that become exposed on removal of the A and B peptides identifies the Ea and Eb sites for intermolecular association. The sequence GPRP, which binds at the Ea site, and the sequence GHRP, which binds at the Eb site, are found in the expected sites as labeled in Figure 7.27B, where they look much like black dots in this whole-molecule view. 

When blood coagulates, the soluble fibrinogen converts into insoluble fibrin. Fibrinogen has a molar mass of about 330 000 g/mol. It consists of a double helix 1.5 nm in diameter with a 6-nm-diameter, globulinlike section at both ends and one of 5 nm in diameter in the center. Through the action of thrombin, two so-called B-peptides with Af = 2 460 g/mol are eliminated from the central part and two A peptides having M = 1 890 g/mol from one of the ends. In a sequence of reactions that remains to be fully explained, this activated fibrinogen is then converted into fibrin. 

Fibrinopeptides the two pairs of peptides (A and B) cleaved from the /V-termini of the 2a and 2P chains of fibrinogen by thrombin. F. arise by cleavage of Arg-GIy bon so that Arg is the C-terminal end of the F, and Gly is the A/-terminal end of the a and P chains of fibrin. Human FA. is Ala-Asp-Ser-Gly-Glu-Gly-Asp-Phe-Leu-Ala-Glu-(Gly)3-Val-Arg, and human F.B. is Pyr-Glu-Gly-Val-Asn-Asp-Asn-(Glu)2-Gly-(Phe)2-Ser-Ala-Arg. F.A. ranges in size from 14 amino acids (horse, lizard) to 19 (cattle), and F.B. from 9 (rhesus monkeys) to 21 (cattle, elk and kangaroo). The sequences of the F. have been used to establish a detailed phylogenetic tree for mammals which is very similar to the classical one. The F. have a vasoconstrictive effect which serves to keep the coagulation principles from being removed too quickly from an injury site. 

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