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. 1976 Mar;57(3):782–790. doi: 10.1172/JCI108337

Studies on the structural abnormality of fibrinogen Paris I.

M W Mosesson, D L Amrani, D Ménaché
PMCID: PMC436714  PMID: 1249208

Abstract

The structural properties of an inherited fibrinogen abnormality designated fibrinogen Paris I were investigated. Dodecyl sulfate gel electrophoresis of unreduced samples revealed no discernible differences in molecular weight from normal; this implied that in fibrinogen Paris I, the normal fibrinogen architecture of six covalently linked chains per molecule is preserved. Examination of dithiothreitol reduced samples before and after treatment with Reptilase or thrombin revealed that the Aalpha- and Bbeta-chains could release the A and B peptides, respectively. A mutant chain (mol wt 52,500, termed gammaParis I) which replaces a large proportion of gamma-chains (mol wt 49,400) was shown, like normal gamma-chains, to lack thrombin- and Reptilase-sensitive sites. The gamma-chains and alpha-chains of Paris I fibrin underwent Factor XIIIa-catalyzed cross-linking slowly; this behavior was not attributable to an intrinsic abnormality of these chains themselves but rather to the inhibitory effect of the mutant gammaParis I chains on this process. Results of DEAE-cellulose gradient elution chromatography of Paris I fibrinogen preparations revealed the presence of small amounts of normal fibrinogen molecules and also indicated that the gammaParis I chains possessed structural overlap with gamma-chains. Unlike gamma-chains however, the gammaParis I chains did not incorporate dansylcadaverine in the prescence of Factor XIIIa, nor, as previously reported, did they undergo cross-linking. The observations indicate that the amine acceptor site found in the COOH-terminal region of the gamma-chain is either not present on the gammaParis I chain or is unavailable for cross-linking. Further support for localization of the abnormality in the COOH-terminal region of the molecule was obtained from the observation that during plasmic hydrolysis of Paris I fibrinogen, at least one unique form of core Fragment D (DParis I) was evolved, whereas Fragment E did not differ from normal.

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