Delayed intermolecular gamma-chain cross-linking by factor XIIIa in fibrinogen Asahi characterized by a gamma-Met-310 to Thr substitution with an N-glycosylated gamma-Asn-308.
In an abnormal fibrinogen with gamma-Met-310 to Thr substitution accompanied by an extra oligosaccharide attached to gamma-Asn-308, factor-XIIIa-mediated intermolecular gamma-dimer formation of fibrin was found to be markedly delayed. The delayed gamma-dimer formation was not due to impaired fibrin polymerization because the fibrinogen gamma-chain also failed to be efficiently cross-linked by factor XIIIa. Since fluorescent amine was normally incorporated into the abnormal gamma-chain by factor XIIIa, we conclude that the abnormal molecules were unable to align their gamma-chains in an anti-parallel fashion because of inaccessibility of the molecules with a profoundly perturbed conformation near the carboxyl terminal region of the gamma-chain included in the D domain.
Yamazumi
K
K
Division of Hemostasis and Thrombosis Research, Jichi Medical School, Tochigi, Japan.
Shimura
K
K
Maekawa
H
H
Muramatsu
S
S
Terukina
S
S
Matsuda
M
M
D005340:Fibrinogen / Q000378:metabolism*; D015241:Fibrinogens, Abnormal / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D015394:Molecular Structure; D011487:Protein Conformation; D011503:Transglutaminases / Q000378:metabolism*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D015241:Fibrinogens, Abnormal; D005353:Fibronectins; D000979:alpha-2-Antiplasmin; C059379:fibrinogen Asahi; C027539:fibrinopeptides gamma; D005340:Fibrinogen; D011503:Transglutaminases