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

Alberto Sala, Stefano Capaldi, Monica Campagnoli, Beniamino Faggion, Sara Labò, Massimiliano Perduca, Assunta Romano, Maria E. Carrizo, Maurizia Valli, Livia Visai, Lorenzo Minchiotti, Monica Galliano, Hugo L. Monaco

Research output: Contribution to journalArticle

Abstract

Insulin-like growth factor (IGF)-bindingprotein-1 (IG-FBP-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 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.

Original languageEnglish
Pages (from-to)29812-29819
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number33
DOIs
Publication statusPublished - Aug 19 2005

ASJC Scopus subject areas

  • Biochemistry

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    Sala, A., Capaldi, S., Campagnoli, M., Faggion, B., Labò, S., Perduca, M., Romano, A., Carrizo, M. E., Valli, M., Visai, L., Minchiotti, L., Galliano, M., & Monaco, H. L. (2005). Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid. Journal of Biological Chemistry, 280(33), 29812-29819. https://doi.org/10.1074/jbc.M504304200