scholarly journals Characterization of the functional defect in factor IX Alabama. Evidence for a conformational change due to high affinity calcium binding in the first epidermal growth factor domain.

1990 ◽  
Vol 265 (18) ◽  
pp. 10250-10254 ◽  
Author(s):  
D M McCord ◽  
D M Monroe ◽  
K J Smith ◽  
H R Roberts
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Conformational Change ◽  
Calcium Binding ◽  
Factor Ix ◽  
Epidermal Growth Factor Domain ◽  
High Affinity ◽  
Functional Defect ◽  
Epidermal Growth

scholarly journals A Gly → Ser Change Causes Defective Foldingin Vitroof Calcium-binding Epidermal Growth Factor-like Domains from Factor IX and Fibrillin-1

1998 ◽  
Vol 273 (14) ◽  
pp. 7807-7813 ◽  
Author(s):  
Pat Whiteman ◽  
A. Kristina Downing ◽  
Rachel Smallridge ◽  
Peter R. Winship ◽  
Penny A. Handford
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Calcium Binding ◽  
Factor Ix ◽  
Fibrillin 1 ◽  
Epidermal Growth

Fibrin Affinity and Clearance of t-PA Deletion and Substitution Analogues

1990 ◽  
Vol 63 (01) ◽  
pp. 054-059 ◽  
Author(s):  
M Johannessen ◽  
V Diness ◽  
K Pingel ◽  
L C Petersen ◽  
D Rao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Half Life ◽  
Consensus Sequence ◽  
Factor Ix ◽  
Tissue Type ◽  
Clot Lysis ◽  
Epidermal Growth Factor Domain ◽  
Epidermal Growth

SummaryTo investigate structure-function relationships in tissue-type plasminogen activator (t-PA) we deleted the following domains in the heavy chain: a) The epidermal growth factor domain (t-PA del. G), b) the finger domain, and the epidermal growth factor domain (t-PA del. FG), and c) the finger, the epidermal growth factor and Kr-ingle 1 (1-PA del, FGK1). To study specificly the function of the growth factor domain we made two substitutions of d) 8 amino acids (consensus sequence) in the growth factor domain (t-PA G-CS) and c) the whole domain with factor IX growth factui doniuin (t-PA G-IX). Finally, f) an analogue with substitution in the finger domain (fibronectin consensus sequence) was constructed (t-PA F-CS).A reduced fibrin binding of all the analogues was found. The fibrin stimulated activity of all analogues was also reduced and correlated to the fibrin binding. In contrast, the activity of the analogues in the clot lysis assay and the plate assay were only slightly reduced as compared to authentic t-PA. This suggested that at high fibrin concentrations the decreased fibrin affinity was less ciitical for obtaining a high fibrinolytic activity.All analogues had a prolonged half-life in vivo as compared to authentic t-PA. The assumption of clearance mechanism involving mainly the growth factor region (or Kringlc 1) was not challenged by the observation of a prolonged half-life for the substitution analogue t-PA F-CS.Our results indicate that a high affinity for fibrin and rapid elimination in vivo of t-PA require a nearly intact conformation of the N-terminal part of the molecule.

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