PMID:17305365
| Citation |
Chandrashekaran, IR, Yao, S, Wang, CC, Bansal, PS, Alewood, PF, Forbes, BE, Wallace, JC, Bach, LA and Norton, RS (2007) The N-terminal subdomain of insulin-like growth factor (IGF) binding protein 6. Structure and interaction with IGFs. Biochemistry 46:3065-74 |
|---|---|
| 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. |
| Links |
PubMed Online version:10.1021/bi0619876 |
| Keywords |
Amino Acid Sequence; Insulin-Like Growth Factor Binding Protein 6/chemistry; Insulin-Like Growth Factor Binding Protein 6/metabolism; Insulin-Like Growth Factor I/metabolism; Insulin-Like Growth Factor II/metabolism; Lanthanoid Series Elements/metabolism; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments/chemical synthesis; Protein Structure, Tertiary; Somatomedins/metabolism |
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