1BOE

STRUCTURE OF THE IGF BINDING DOMAIN OF THE INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 (IGFBP-5): IMPLICATIONS FOR IGF AND IGF-I RECEPTOR INTERACTIONS

Summary for 1BOE

• Entry DOI: 10.2210/pdb1boe/pdb
• Descriptor: PROTEIN (INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 (IGFBP-5)) (1 entity in total)
• Functional Keywords: mini-igfbp-5, igfbp-5, igf, insulin-like growth factor binding protein, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 5208.93

Authors

Kalus, W.,Zweckstetter, M.,Renner, C.,Sanchez, Y.,Georgescu, J.,Grol, M.,Demuth, D.,Schumacherdony, C.,Lang, K.,Holak, T.H. (deposition date: 1998-07-30, release date: 1998-12-16, Last modification date: 2022-02-16)

Primary citation

Kalus, W.,Zweckstetter, M.,Renner, C.,Sanchez, Y.,Georgescu, J.,Grol, M.,Demuth, D.,Schumacher, R.,Dony, C.,Lang, K.,Holak, T.A.
Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.
EMBO J., 17:6558-6572, 1998

PubMed Abstract: Binding proteins for insulin-like growth factors (IGFs) IGF-I and IGF-II, known as IGFBPs, control the distribution, function and activity of IGFs in various cell tissues and body fluids. Insulin-like growth factor-binding protein-5 (IGFBP-5) is known to modulate the stimulatory effects of IGFs and is the major IGF-binding protein in bone tissue. We have expressed two N-terminal fragments of IGFBP-5 in Escherichia coli; the first encodes the N-terminal domain of the protein (residues 1-104) and the second, mini-IGFBP-5, comprises residues Ala40 to Ile92. We show that the entire IGFBP-5 protein contains only one high-affinity binding site for IGFs, located in mini-IGFBP-5. The solution structure of mini-IGFBP-5, determined by nuclear magnetic resonance spectroscopy, discloses a rigid, globular structure that consists of a centrally located three-stranded anti-parallel beta-sheet. Its scaffold is stabilized further by two inside packed disulfide bridges. The binding to IGFs, which is in the nanomolar range, involves conserved Leu and Val residues localized in a hydrophobic patch on the surface of the IGFBP-5 protein. Remarkably, the IGF-I receptor binding assays of IGFBP-5 showed that IGFBP-5 inhibits the binding of IGFs to the IGF-I receptor, resulting in reduction of receptor stimulation and autophosphorylation. Compared with the full-length IGFBP-5, the smaller N-terminal fragments were less efficient inhibitors of the IGF-I receptor binding of IGFs.

PubMed: 9822601
DOI: 10.1093/emboj/17.22.6558

Experimental method

SOLUTION NMR