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https://hdl.handle.net/2440/43189
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Type: | Journal article |
Title: | The N-terminal subdomain of insulin-like growth factor (IGF) binding protein 6. Structure and interaction with IGFs |
Author: | Chandrashekaran, I. Yao, S. Wang, C. Bansal, P. Alewood, P. Forbes, B. Wallace, J. Bach, L. Norton, R. |
Citation: | Biochemistry, 2007; 46(11):3065-3074 |
Publisher: | Amer Chemical Soc |
Issue Date: | 2007 |
ISSN: | 0006-2960 1520-4995 |
Statement of Responsibility: | Indu R. Chandrashekaran, Shenggen Yao, Chunxiao C. Wang, Paramjit S. Bansal, Paul F. Alewood, Briony E. Forbes, John C. Wallace, Leon A. Bach, and Raymond S. Norton |
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 -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. |
Keywords: | Lanthanoid Series Elements Somatomedins Insulin-Like Growth Factor I Insulin-Like Growth Factor II Peptide Fragments Insulin-Like Growth Factor Binding Protein 6 Nuclear Magnetic Resonance, Biomolecular Amino Acid Sequence Protein Structure, Tertiary Molecular Sequence Data |
Description: | Copyright © 2007 American Chemical Society |
DOI: | 10.1021/bi0619876 |
Published version: | http://dx.doi.org/10.1021/bi0619876 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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