2JM2

Structure of the N-terminal subdomain of insulin-like growth factor (IGF) binding protein-6 and its interactions with IGFs

Summary for 2JM2

• Entry DOI: 10.2210/pdb2jm2/pdb
• NMR Information: BMRB: 7262
• Descriptor: Insulin-like growth factor-binding protein 6 (1 entity in total)
• Functional Keywords: insulin like growth factor binding protein, growth factor, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 4368.76

Authors

Chandrashekaran, I.R.,Yao, S.,Wang, C.C.,Bansal, P.S.,Alewood, P.F.,Forbes, B.E.,Wallace, J.C.,Bach, L.A.,Norton, R.S. (deposition date: 2006-09-18, release date: 2007-03-27, Last modification date: 2024-11-20)

Primary citation

Chandrashekaran, I.R.,Yao, S.,Wang, C.C.,Bansal, P.S.,Alewood, P.F.,Forbes, B.E.,Wallace, J.C.,Bach, L.A.,Norton, R.S.
The N-Terminal Subdomain of Insulin-like Growth Factor (IGF) Binding Protein 6. Structure and Interaction with IGFs
Biochemistry, 46:3065-3074, 2007

PubMed Abstract: Insulin-like growth factor binding proteins (IGFBPs) modulate the activity and distribution of insulin-like growth factors (IGFs). IGFBP-6 differs from other IGFBPs in being a relatively specific inhibitor of IGF-II actions. Another distinctive feature of IGFBP-6 is its unique N-terminal disulfide linkages; the N-domains of IGFBPs 1-5 contain six disulfides and share a conserved GCGCC motif, but IGFBP-6 lacks the two adjacent cysteines in this motif, so its first three N-terminal disulfide linkages differ from those of the other IGFBPs. The contributions of the N- and C-domains of IGFBP-6 to its IGF binding properties and their structure-function relationships have been characterized in part, but the structure and function of the distinctive N-terminal subdomain of IGFBP-6 are unknown. Here we report the solution structure of a polypeptide corresponding to residues 1-45 of the N-terminal subdomain of IGFBP-6 (NN-BP-6). The extended structure of the N-terminal subdomain of IGFBP-6 is very different from that of the short two-stranded beta-sheet of the N-terminal subdomain of IGFBP-4 and, by implication, the other IGFBPs. NN-BP-6 contains a potential cation-binding motif; lanthanide ion binding was observed, but no significant interaction was found with physiologically relevant metal ions like calcium or magnesium. However, this subdomain of IGFBP-6 has a higher affinity for IGF-II than IGF-I, suggesting that it may contribute to the marked IGF-II binding preference of IGFBP-6. The extended structure and flexibility of this subdomain of IGFBP-6 could play a role in enhancing the rate of ligand association and thereby be significant in IGF recognition.

PubMed: 17305365
DOI: 10.1021/bi0619876

Experimental method

SOLUTION NMR