Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid.
Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) regulates the activity of the insulin-like growth factors in early pregnancy and is, thus, thought to play a key role at the fetal-maternal interface. The C-terminal domain of IGFBP-1 and three isoforms of the intact protein were isolated from human amniotic fluid, and sequencing of the four N-terminal polypeptide chains showed them to be highly pure. The addition of both intact IGFBP-1 and its C-terminal fragment to cultured fibroblasts has a similar stimulating effect on cell migration, and therefore, the domain has a biological activity on its own. The three-dimensional structure of the C-terminal domain was determined by x-ray crystallography to 1.8 Angstroms resolution. The fragment folds as a thyroglobulin type I domain and was found to bind the Fe(2+) ion in the crystals through the only histidine residue present in the polypeptide chain. Iron (II) decreases the binding of intact IGFBP-1 and the C-terminal domain to IGF-II, suggesting that the metal binding site is close to or part of the surface of interaction of the two molecules.
Department of Biochemistry A. Castellani, University of Pavia, Italy.
Alberto
A
Sala
Stefano
S
Capaldi
Monica
M
Campagnoli
Beniamino
B
Faggion
Sara
S
Labò
Massimiliano
M
Perduca
Assunta
A
Romano
Maria E
ME
Carrizo
Maurizia
M
Valli
Livia
L
Visai
Lorenzo
L
Minchiotti
Monica
M
Galliano
Hugo L
HL
Monaco
D000595:Amino Acid Sequence; D000653:Amniotic Fluid / Q000737:chemistry*; D002465:Cell Movement; D018360:Crystallography, X-Ray; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000737:chemistry*; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D018970:Insulin-Like Growth Factor Binding Protein 1; D007501:Iron