Binding site for the C-domain of insulin-like growth factor (IGF) binding protein-6 on IGF-II; implications for inhibition of IGF actions.
Insulin-like growth factors (IGFs) are important mediators of growth and IGF-binding proteins (IGFBPs) 1-6 regulate IGF actions. As IGFBP C-terminal domains contribute to high-affinity IGF binding, we have defined the binding site for the C-domain of IGFBP-6 on IGF-II using NMR. This site lies adjacent to and between the binding sites for the IGFBP N-domain and IGF-I receptor (IGFIR), which have previously been found on opposite sides of the IGF molecule. The C-domain is therefore likely to interfere with IGF binding to the IGFIR, providing a structural basis for the potent inhibitory effects of intact IGFBPs on IGF actions.
Headey
Stephen J
SJ
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Australia.
Keizer
David W
DW
Yao
Shenggen
S
Wallace
John C
JC
Bach
Leon A
LA
Norton
Raymond S
RS
D001665:Binding Sites; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular
D018976:Insulin-Like Growth Factor Binding Protein 6; D007335:Insulin-Like Growth Factor II