Structural basis for the regulation of insulin-like growth factors by IGF binding proteins

Siwanowicz, Igor, Popowicz, Grzegorz M., Wisniewska, Magdalena, Huber, Robert, Kuenkele, Klaus-Peter, Lang, Kurt, Engh, Richard A. and Holak, Tad A. 2005. Structural basis for the regulation of insulin-like growth factors by IGF binding proteins. Structure 13 (1) , pp. 155-167. 10.1016/j.str.2004.11.009

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Abstract

Insulin-like growth factor binding proteins (IGFBPs) control the extracellular distribution, function, and activity of IGFs. Here, we report an X-ray structure of the binary complex of IGF-I and the N-terminal domain of IGFBP-4 (NBP-4, residues 3–82) and a model of the ternary complex of IGF-I, NBP-4, and the C-terminal domain (CBP-4, residues 151–232) derived from diffraction data with weak definition of the C-terminal domain. These structures show how the IGFBPs regulate IGF signaling. Key features of the structures include (1) a disulphide bond ladder that binds to IGF and partially masks the IGF residues responsible for type 1 IGF receptor (IGF-IR) binding, (2) the high-affinity IGF-I interaction site formed by residues 39–82 in a globular fold, and (3) CBP-4 interactions. Although CBP-4 does not bind individually to either IGF-I or NBP-4, in the ternary complex, CBP-4 contacts both and also blocks the IGF-IR binding region of IGF-I.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QR Microbiology
Publisher:	Elsevier
ISSN:	0969-2126
Last Modified:	24 Jun 2017 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/70013

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