A central domain binding site in insulin-like growth factor binding protein-5 for the acid-labile subunit

Like insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-5 forms a ternary complex with insulin-like growth factor (IGF)-I or ICE-Il, and th e acid-labile subunit (ALS). The study of IGFBP-5/IGFBP-6 chimeric proteins with amino-terminal and middle domain swaps, has revealed the existence of a site in the middle domain of IGFBP-5, that binds to ALS in the absence o f the IGFBP-5 carboxy-terminal domain. An IGFBP-6 chimeric protein containi ng the central domain of IGFBP-5 complexed efficiently with ALS, and a carb oxy-terminally truncated IGFBP-5 mutant, IGFBP-5(1-169), also bound to ALS in the presence of IGFs, although with much less potency than full length r hIGFBP-5. In contrast to the latter, IGFBP-5(1-169) preferentially formed t ernary complexes with IGF-II rather than IGF-I. These results indicate that a site which binds ALS exists in IGFBP-5 mutants which lack the IGFBP-5 ca rboxy-terminal domain.