Binding site for the C-domain of insulin-like growth factor (IGF) binding protein-6 on IGF-II; implications for inhibition of IGF actions

Stephen J Headey; David W Keizer; Shenggen Yao; John C Wallace; Leon A Bach; Raymond S Norton

doi:10.1016/j.febslet.2004.04.091

Binding site for the C-domain of insulin-like growth factor (IGF) binding protein-6 on IGF-II; implications for inhibition of IGF actions

FEBS Lett. 2004 Jun 18;568(1-3):19-22. doi: 10.1016/j.febslet.2004.04.091.

Authors

Stephen J Headey¹, David W Keizer, Shenggen Yao, John C Wallace, Leon A Bach, Raymond S Norton

Affiliation

¹ The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Australia.

PMID: 15196913
DOI: 10.1016/j.febslet.2004.04.091

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Insulin-Like Growth Factor Binding Protein 6 / metabolism*
Insulin-Like Growth Factor II / antagonists & inhibitors
Insulin-Like Growth Factor II / chemistry
Insulin-Like Growth Factor II / metabolism*
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular

Substances

Insulin-Like Growth Factor Binding Protein 6
Insulin-Like Growth Factor II