The polymerization of fibrinogen Dusart (A alpha 554 Arg-->Cys) after removal of carboxy terminal regions of the A alpha-chains.
The six polypeptide chains of normal fibrinogen are covalently linked by interchain disulphide bonds, and there are no free sulphydryl groups. Fibrinogen Dusart is a congenital fibrinogen variant in which A alpha 554 Arg is replaced by Cys; albumin is disulphide linked to these fibrinogen molecules, possibly at A alpha 554 Cys. Functionally, Dusart fibrinogen displays markedly abnormal fibrin polymerization, characterized by delayed lateral fibril association and matrix fibre bundles that are thinner than normal fibrin bundles. These observations are consistent with experiments suggesting that the carboxy terminal region of the A alpha-chain contains a polymerization domain that participates in lateral fibril associations. In order to investigate the location and the effect of albumin binding to Dusart fibrinogen, we examined the fibrinogen by electron microscopy, and compared the polymerization and ultrastructure of fibrin prepared from normal fibrinogen containing intact A alpha-chains (fraction I-2) or plasmin degraded fibrinogen molecules lacking carboxy terminal regions of A alpha-chains (fraction I-9D), with fibrin prepared from Dusart fraction I-2 and I-9D. Most bound albumin was released from Dusart fibrinogen by plasmin degradation involving the A alpha-chains. Nevertheless, we were able to visualize albumin molecules remaining covalently bound to Dusart I-9D as well as to Dusart I-2 fibrinogen, as distinct globular domains situated near the fibrinogen D domain. The presence of albumin in these fractions was confirmed by Western blotting using anti-albumin. Dusart fibrin polymerized much more slowly than normal I-2, as previously reported, whereas polymerization of Dusart I-9D fibrin was faster than Dusart I-2 and nearly the same as normal I-9D fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)
Siebenlist
K R
KR
University of Wisconsin Medical School, Milwaukee 53233.
Mosesson
M W
MW
DiOrio
J P
JP
Soria
J
J
Soria
C
C
Caen
J P
JP
D000418:Albumins / Q000737:chemistry; D001120:Arginine; D003553:Cystine; D005337:Fibrin / Q000737:chemistry / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry* / Q000235:genetics; D015241:Fibrinogens, Abnormal / Q000737:chemistry*; D015394:Molecular Structure; D011108:Polymers
D000418:Albumins; D015241:Fibrinogens, Abnormal; D011108:Polymers; D003553:Cystine; D005337:Fibrin; D005340:Fibrinogen; D001120:Arginine