Structure, Dynamics and Heparin Binding of the C-terminal Domain of Insulin-like Growth Factor-binding Protein-2 (IGFBP-2)

2006 ◽  
Vol 364 (4) ◽  
pp. 690-704 ◽  
Author(s):  
Zhihe Kuang ◽  
Shenggen Yao ◽  
David W. Keizer ◽  
Chunxiao C. Wang ◽  
Leon A. Bach ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Structure Dynamics ◽  
Terminal Domain

OR04-3 C-TERMINAL DOMAIN OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-2 (IGFBP-2): STRUCTURE, DYNAMICS AND INTERACTION WITH IGFS

2006 ◽  
Vol 16 ◽  
pp. S7
Author(s):  
Briony E Forbes ◽  
Zhihe Kuang ◽  
Shenggen Yao ◽  
David W Keizer ◽  
Chunxiao C Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Structure Dynamics ◽  
Terminal Domain

Insulin-like growth factor binding protein-2: NMR analysis and structural characterization of the N-terminal domain

Biochimie ◽  
2012 ◽  
Vol 94 (3) ◽  
pp. 608-616 ◽  
Author(s):  
Charles A. Galea ◽  
Mehdi Mobli ◽  
Kerrie A. McNeil ◽  
Terrence D. Mulhern ◽  
John C. Wallace ◽  
...  
Keyword(s):  
Growth Factor ◽  
Structural Characterization ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Nmr Analysis ◽  
Factor Binding ◽  
Terminal Domain

scholarly journals Ligand-binding characteristics of recombinant amino- and carboxyl-terminal fragments of human insulin-like growth factor-binding protein-3

2001 ◽  
Vol 169 (1) ◽  
pp. 123-133 ◽  
Author(s):  
M Galanis ◽  
SM Firth ◽  
J Bond ◽  
A Nathanielsz ◽  
AA Kortt ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Igf I ◽  
Igf Binding ◽  
Carboxyl Terminal ◽  
Igfbp 3

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a member of a family of structurally conserved proteins (IGFBP-1 to -6) which act as carriers and regulators of the mitogenic peptide hormones IGF-I and IGF-II. Members of the IGFBP family share conserved cysteine-rich amino- and carboxyl-terminal regions. The amino-terminal domain of these proteins is recognised to contain an IGF-binding determinant, but evidence to support a binding site in the carboxyl-terminal region of the protein is less rigorous. To further investigate this, we have synthesised both the amino-terminal (residues 1-88; N-88) and carboxyl-terminal (residues 165-264; C-165) domains of human IGFBP-3 in bacteria, as fusion proteins with a carboxyl-terminal FLAG peptide. Although only C-165 showed binding to IGF-I and -II by solution-binding assays, both N-88 and C-165 demonstrated binding to IGF-I and -II by biosensor analysis albeit with reduced affinities compared with full-length IGFBP-3. Only the carboxyl-terminal fragment (C-165) was able to form hetero-trimeric complexes with IGF-I and the acid-labile subunit (ALS). We conclude that the carboxyl-terminal domain of IGFBP-3 contains an IGF-binding determinant and can form ternary complexes with ALS.

IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis

2002 ◽  
Vol 282 (1) ◽  
pp. E52-E58 ◽  
Author(s):  
B. A. Booth ◽  
M. Boes ◽  
B. L. Dake ◽  
K. L. Knudtson ◽  
R. S. Bar
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Binding Protein ◽  
Vascular Endothelial ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Binding Region ◽  
Factor Binding ◽  
Igfbp 3

Insulin-like growth factor-binding protein (IGFBP)-3 contains a highly basic COOH-terminal heparin-binding region, the P3 region, which is thought to be important in the binding of IGFBP-3 to endothelial cells. IGFBP-3 and IGFBP-4, and their chimeras IGFBP-34 and IGFBP-43, were treated with plasmin and with thrombin, proteases known to cleave IGFBP-3. IGFBP-3 was highly susceptible to plasmin, whereas IGFBP-4 was less so. Substitution of the P3 region for the P4 region in IGFBP-4 (IGFBP-43) increased the ability of the protease to digest IGFBP-43; substitution of the P4 region for the P3 region in IGFBP-3 (IGFBP-34) decreased the digestion of IGFBP-34. When 125I-labeled IGFBP-3 or125I-IGFBP-43 was first bound to vascular endothelial cells, subsequent proteolysis by either plasmin or thrombin was substantially inhibited. Proteolysis of125I-IGFBP-34 was not inhibited in the presence of endothelial cells. The P3 peptide was cleaved by plasmin but not by thrombin. We conclude that the P3 region is central to proteolysis of IGFBP-3 by plasmin and thrombin, processes which were inhibited by association of IGFBP-3 with endothelial cells.

Insulin-Like Growth Factor Binding Protein-2: Contributions of the C-Terminal Domain to Insulin-Like Growth Factor-1 Binding

2005 ◽  
Vol 69 (3) ◽  
pp. 833-845 ◽  
Author(s):  
Megan M. Kibbey ◽  
Mark J. Jameson ◽  
Erin M. Eaton ◽  
Steven A. Rosenzweig
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Terminal Domain

Plasmin degradation of insulin-like growth factor-binding protein-5 (IGFBP-5): regulation by IGFBP-5-(201—218)

1997 ◽  
Vol 273 (5) ◽  
pp. E996-E1004 ◽  
Author(s):  
Phil G. Campbell ◽  
Dennis L. Andress
Keyword(s):  
Growth Factor ◽  
Solid Phase ◽  
Binding Protein ◽  
Competitive Inhibitor ◽  
Binding Domain ◽  
Tissue Type ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Heparin Binding Domain

Using the major bone insulin-like growth factor-binding protein (IGFBP) IGFBP-5, we took a mechanistic approach in evaluating the role of the heparin-binding domain of IGFBP-5 in regulating plasmin (Pm) proteolysis of IGFBP-5. Using synthetic IGFBP-5 peptide fragments, we determined that the heparin-binding domain, IGFBP-5-(208—218), inhibits Pm proteolysis of intact IGFBP-5. The mechanism of action of IGFBP-5-(201—218) was by inhibiting Pm binding to substrate IGFBP-5. IGFBP-5-(201—218) action was independent of site of proteolysis, fluid, or solid phase interaction. In addition, IGFBP-5-(201—218) was found to inhibit plasminogen (Pg) activation to Pm. IGFBP-5-(201—218) did not directly inhibit the activity of Pm, urokinase Pg activator (PA), or tissue-type PA but acted as a competitive inhibitor of Pg activation by PA, which is in contrast to the stimulating effect of heparin on Pg activation. These data indicate that the heparin-binding domain contains the serine protease (Pg-to-Pm) binding site region of IGFBP-5, and that this region, which is presumed to represent a Pm-induced proteolytic product of IGFBP-5, is capable of regulating Pm action.

IGFBP-3 proteolysis by plasmin, thrombin, serum: heparin binding, IGF binding, and structure of fragments

1996 ◽  
Vol 271 (3) ◽  
pp. E465-E470 ◽  
Author(s):  
B. A. Booth ◽  
M. Boes ◽  
R. S. Bar
Keyword(s):  
Growth Factor ◽  
Endothelial Function ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Endothelial Surface ◽  
Igf Binding ◽  
Heparin Affinity ◽  
Igfbp 3

Insulin-like growth factor binding protein (IGFBP)-3 was exposed to plasmin, thrombin, and pregnancy serum, substances normally present at the endothelial surface in enriched concentrations. The NH2-termini of the proteolytic fragments were sequenced, and their ability to bind insulin-like growth factor (IGF) and heparin was assessed by ligand blotting. Plasmin generated at least five fragments, three beginning at the NH2-terminus of IGFBP-3 and two with NH2-termini corresponding to middle portions of IGFBP-3. The dominant fragment bound both IGF and heparin while NH2-terminal fragments bound only IGF. Thrombin generated three and serum five easily identified fragments; the dominant fragments, beginning at midportions of IGFBP-3, retained IGF and heparin affinity, whereas the remaining fragments had differential affinities for IGF and heparin. We suggest that such fragments, when generated at the endothelia surface, have the potential to alter regional vascular concentrations of IGF and thus influence both IGF and endothelial function.

scholarly journals Structure and Properties of the C-terminal Domain of Insulin-like Growth Factor-binding Protein-1 Isolated from Human Amniotic Fluid

2005 ◽  
Vol 280 (33) ◽  
pp. 29812-29819 ◽  
Author(s):  
Alberto Sala ◽  
Stefano Capaldi ◽  
Monica Campagnoli ◽  
Beniamino Faggion ◽  
Sara Labò ◽  
...  
Keyword(s):  
Growth Factor ◽  
Amniotic Fluid ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Structure And Properties ◽  
Human Amniotic Fluid ◽  
Factor Binding ◽  
Terminal Domain
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