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

SALA, ALBERTO; CAPALDI, STEFANO; CAMPAGNOLI, MONICA; FAGGION, BENIAMINO; LABÒ, SARA; PERDUCA, MASSIMILIANO; ROMANO, ASSUNTA; CARRIZO, MARÍA E.; VALLI, MAURIZIA; VISAI, LIVIA; MINCHIOTTI, LORENZO; GALLIANO, MONICA; MONACO, HUGO L.

JOURNAL OF BIOLOGICAL CHEMISTRY

American Society for Biochemistry and Molecular Biology

Lugar: Baltimore; Año: 2005 vol. 280 p. 29812 - 29819

0021-9258

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.