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.
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
Kevin R
KR
Siebenlist
Michael W
MW
Mosesson
Irene
I
Hernandez
Leslie A
LA
Bush
Enrico
E
Di Cera
John R
JR
Shainoff
James P
JP
Di Orio
Laurie
L
Stojanovic
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