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 Cterminal domain was determined by x-ray crystallography to 1.8 Å resolution. The fragment folds as a thyroglobulin type I domain and was found to bind the Fe2 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.

Structure and properties of the C-terminal domain of insulin-like growth factor binding protein-1 isolated from human amniotic fluid

CAPALDI, Stefano;FAGGION, Beniamino;PERDUCA, Massimiliano;MONACO, Ugo Luigi
2005-01-01

Abstract

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 Cterminal domain was determined by x-ray crystallography to 1.8 Å resolution. The fragment folds as a thyroglobulin type I domain and was found to bind the Fe2 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.
Insulin-like growth factor (IGF)-binding protein-1; C-terminal domain; human amniotic fluid; three-dimensional structure; thyroglobulin type I domain; metal binding site
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/302239
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