Studies on the basis for the properties of fibrin produced from fibrinogen-containing gamma' chains.
Human fibrinogen 1 is homodimeric with respect to its gamma chains (gammaA-gammaA'), whereas fibrinogen 2 molecules each contain one gammaA (gammaA1-411V) and one gamma' chain, which differ by containing a unique C-terminal sequence from gamma'408 to 427L that binds thrombin and factor XIII. We investigated the structural and functional features of these fibrins and made several observations. First, thrombin-treated fibrinogen 2 produced finer, more branched clot networks than did fibrin 1. These known differences in network structure were attributable to delayed release of fibrinopeptide (FP) A from fibrinogen 2 by thrombin, which in turn was likely caused by allosteric changes at the thrombin catalytic site induced by thrombin exosite 2 binding to the gamma' chains. Second, cross-linking of fibrin gamma chains was virtually the same for both types of fibrin. Third, the acceleratory effect of fibrin on thrombin-mediated XIII activation was more prominent with fibrin 1 than with fibrin 2, and this was also attributable to allosteric changes at the catalytic site induced by thrombin binding to gamma' chains. Fourth, fibrinolysis of fibrin 2 was delayed compared with fibrin 1. Altogether, differences between the structure and function of fibrins 1 and 2 are attributable to the effects of thrombin binding to gamma' chains.
Siebenlist
Kevin R
KR
Department of Biomedical Sciences, College of Health Sciences, Marquette University, Schroeder Health Complex, 426, PO Box 1881, Milwaukee, WI 53233-1881, USA. kevin.siebenlist@marquette.edu
Mosesson
Michael W
MW
Hernandez
Irene
I
Bush
Leslie A
LA
Di Cera
Enrico
E
Shainoff
John R
JR
Di Orio
James P
JP
Stojanovic
Laurie
L
D005176:Factor XIII / Q000378:metabolism; D005337:Fibrin / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D005342:Fibrinolysis; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
D011498:Protein Precursors; C027539:fibrinopeptides gamma; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D013917:Thrombin