胰岛素样生长因子（IGF）结合蛋白-6的C结构域在IGF-II上的结合位点；对IGF作用抑制的影响。

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

作者信息

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

机构信息

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

出版信息

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

DOI:10.1016/j.febslet.2004.04.091

PMID:15196913

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.

摘要

胰岛素样生长因子（IGFs）是生长的重要介质，而胰岛素样生长因子结合蛋白（IGFBPs）1 - 6调节IGF的作用。由于IGFBP的C末端结构域有助于与IGF高亲和力结合，我们利用核磁共振（NMR）确定了IGFBP - 6的C结构域在IGF - II上的结合位点。该位点位于IGFBP N结构域和IGF - I受体（IGFIR）结合位点的相邻处且在两者之间，此前已发现IGFBP N结构域和IGFIR的结合位点位于IGF分子的相对两侧。因此，C结构域可能会干扰IGF与IGFIR的结合，为完整的IGFBPs对IGF作用的强效抑制作用提供了结构基础。