Sm. Firth et al., Mutagenesis of basic amino acids in the carboxyl-terminal region of insulin-like growth factor binding protein-5 affects acid-labile subunit binding, ENDOCRINOL, 142(5), 2001, pp. 2147-2150
Like insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-5 was re
cently shown to form ternary complexes with insulin-like growth factor (IGF
) and the acid-labile subunit (ALS). Previous studies using IGFBP-5/IGFBP-6
chimeric proteins have identified major and minor ALS binding sites in the
carboxyl-terminal and central regions, respectively of IGFBP-5. We now rep
ort that ALS binds to IGFBP-3 (K-a = 1.1 +/- 0.1 liters/nmol) and IGFBP-5 (
K-a = 1.8 +/- 0.5 liters/nmol) with similar binding affinities. Using site-
specific mutants, we have identified residues K-211/R-214/K-217/R-218 withi
n the carboxyl-terminal region of IGFBP-5 as being essential for ALS bindin
g. Mutation of (KR136)-R-134 or (KK139)-K-138 in the central region of IGFB
P-5 resulted in a small decrease in ALS binding.