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 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.