C-terminal domain of insulin-like growth factor (IGF) binding protein-6: Structure and interaction with IGF-II

Abstract

IGFs are important mediators of growth. IGF binding proteins (IGFBPs) 1-6 regulate IGF actions and have IGF-independent actions. The C-terminal domains of IGFBPs contribute to high-affinity IGF binding and modulation of IGF actions and confer some IGF-independent properties, but understanding how they achieve this has been constrained by the lack of a three-dimensional structure. We therefore determined the solution structure of the C-domain of IGFBP-6 using nuclear magnetic resonance (NMR). The domain consists of a thyroglobulin type 1 fold comprising an α-helix followed by a loop, a three-stranded anti-parallel β-sheet incorporating a second loop, and finally a disulfide-bonded flexible th..