Conformation of the carboxy-terminal region of the Aalpha chain of fibrinogen as elucidated by immunochemical analyses
Open Access
- 1 June 1984
- journal article
- research article
- Published by Wiley in European Journal of Biochemistry
- Vol. 141 (3) , 489-496
- https://doi.org/10.1111/j.1432-1033.1984.tb08219.x
Abstract
The conformation of the carboxy-terminal aspects of the A.alpha. chain of human fibrinogen was assessed by immunochemically characterizing the A.alpha. 239-476 and A.alpha. 518-584 regions of the molecule. Two peptides, corresponding to these regions, were isolated from cyanogen bromide digests of the A.alpha. chain by molecular exclusion and high-performance liquid chromatography. Each peptide reacted with antibodies elicited by immunization with the A.alpha. chain and intact fibrinogen. A.alpha. 239-476 appears to be a relatively immunodominant region of the molecule. Competitive inhibition analyses confirmed the accessibility of these regions to antibody in native fibrinogen. Each peptide, however, contained 1 or more epitopes, which was occult in the native molecule. These occult epitopes were expressed by the intact A.alpha. chain and became accessible when fibrinogen was cleaved with plasmin. With plasmic degradation the epitopes expressed by fibrinogen and contained within these 2 peptide regions became significantly more reactive with antibody. This change occurred in concert with release of the A.alpha. 518-584 region from the core of the molecule but did not require the generation of free A.alpha. 239-476. Ultimately the epitopes within both regions were shed from the plasmin-resistant core of fibrinogen. Peptide epitopes were expressed in a similar manner by prolonged plasmic degradation of fibrinogen and fibrin with .alpha. chain cross-linking. These results are generally consistent with models depicting the carboxyl-terminal aspects of the A.alpha. chain as being surface-oriented but suggest a systemic ordering of structure when these regions are integrated into the native molecule. Plasmic cleavage significantly relaxes the conformational restraints on the organization within this region.This publication has 38 references indexed in Scilit:
- Monoclonal antibodies to .alpha.-chain regions of human fibrinogen that participate in polymer formationBiochemistry, 1983
- Prediction of protein antigenic determinants from amino acid sequences.Proceedings of the National Academy of Sciences, 1981
- Amino acid sequence studies on the .alpha. chain of human fibrinogen. Complete sequence of the largest cyanogen bromide fragmentBiochemistry, 1979
- Trinodular structure of fibrinogenJournal of Molecular Biology, 1979
- Amino acid sequence studies on the α chain of human fibrinogen. Isolation and characterization of two linked α-chain cyanogen bromide fragments from fully cross-linked fibrinBiochemistry, 1977
- The amino acid sequence of a 27-residue peptide feleased from the α-chain carboxy-terminus during the plasmic digestion of human fibrinogenBiochemical and Biophysical Research Communications, 1976
- Antigenic Structure of the Cyanogen Bromide Peptide F‐CB3 from Fibrinogen ‐ChainEuropean Journal of Biochemistry, 1975
- Isolation and immunological characterization of a disulfide loop region in human fibrinogen α chainFEBS Letters, 1975
- Antigenic Determinants in the Disulfide Regions of Bovine FibrinogenEuropean Journal of Biochemistry, 1975
- Immunobiology of Fibrinogen. EMERGENCE OF NEOANTIGENIC EXPRESSIONS DURING PHYSIOLOGIC CLEAVAGE IN VITRO AND IN VIVOJournal of Clinical Investigation, 1973