1WQJ

Structural Basis for the Regulation of Insulin-Like Growth Factors (IGFs) by IGF Binding Proteins (IGFBPs)

Summary for 1WQJ

• Entry DOI: 10.2210/pdb1wqj/pdb
• Related: 1H59
• Descriptor: Insulin-like growth factor binding protein 4, Insulin-like growth factor IB (3 entities in total)
• Functional Keywords: protein-protein complex, disulfide rich, disulfide bond ladder, protein binding-hormone-growth factor complex, protein binding/hormone/growth factor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P22692 P05019
• Total number of polymer chains: 2
• Total formula weight: 16161.87

Authors

Siwanowicz, I.,Popowicz, G.M.,Wisniewska, M.,Huber, R.,Kuenkele, K.P.,Lang, K.,Engh, R.A.,Holak, T.A. (deposition date: 2004-09-29, release date: 2005-03-01, Last modification date: 2024-10-23)

Primary citation

Siwanowicz, I.,Popowicz, G.M.,Wisniewska, M.,Huber, R.,Kuenkele, K.P.,Lang, K.,Engh, R.A.,Holak, T.A.
Structural basis for the regulation of insulin-like growth factors by IGF binding proteins
Structure, 13:155-167, 2005

PubMed 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.

PubMed: 15642270
DOI: 10.1016/j.str.2004.11.009

Experimental method

X-RAY DIFFRACTION (1.6 Å)