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.
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.
Yamazumi
K
K
Institute of Hematology, Jichi Medical School, Tochigi, Japan.
Shimura
K
K
Terukina
S
S
Takahashi
N
N
Matsuda
M
M
D000328:Adult; D000595:Amino Acid Sequence; D001216:Asparagine; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D015241:Fibrinogens, Abnormal / Q000302:isolation & purification* / Q000378:metabolism; D006031:Glycosylation; D006474:Hemorrhagic Disorders / Q000097:blood* / Q000151:congenital / Q000235:genetics; D006801:Humans; D008297:Male; D008715:Methionine; D008969:Molecular Sequence Data; D009154:Mutation; D009844:Oligosaccharides; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D013912:Threonine; D013917:Thrombin
D015241:Fibrinogens, Abnormal; D009844:Oligosaccharides; D010446:Peptide Fragments; C059379:fibrinogen Asahi; D013912:Threonine; D001216:Asparagine; D008715:Methionine; D013917:Thrombin