A gamma methionine-310 to threonine substitution and consequent N-glycosylation at gamma asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi.
K Yamazumi, … , N Takahashi, M Matsuda
K Yamazumi, … , N Takahashi, M Matsuda
Published May 1, 1989
Citation Information: J Clin Invest. 1989;83(5):1590-1597. https://doi.org/10.1172/JCI114056.
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Research Article

A gamma methionine-310 to threonine substitution and consequent N-glycosylation at gamma asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi.

Abstract

In an abnormal fibrinogen with severely impaired polymerization of fibrin monomers, we identified a methionine-to-threonine substitution at position 310 of the gamma chain. Furthermore, asparagine at position 308 was found to be N-glycosylated due to a newly formed consensus sequence, asparagine(308)-glycine(309)-threonine(310). The two structural defects in the mutant gamma chain may well perturb the conformation required for fibrin monomer polymerization that is specifically assigned to the D domain of fibrinogen. This alteration also seems to affect the intermolecular gamma chain cross-linking of fibrin and fibrinogen, although the amine acceptor gamma glutamine-398 was found to function normally. These functional abnormalities may well be related to posttraumatic hemorrhage as observed in a 33-yr-old man with moderate hemorrhagic diathesis related to injuries since his early adolescence. The structure of the extra carbohydrate moiety attached to asparagine-308 was found to be identical with those derived from the normal B beta and gamma chains as evidenced by HPLC.

Authors

K Yamazumi, K Shimura, S Terukina, N Takahashi, M Matsuda

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