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https://hdl.handle.net/2440/43767
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Type: | Journal article |
Title: | A novel binding site for the human insulin-like growth factor-II (IGF-II)/mannose 6-phosphate receptor on IGF-II |
Author: | Delaine, C. Alvino, C. McNeil, K. Mulhern, T. Gauguin, L. De Meyts, P. Jones, E. Brown, J. Wallace, J. Forbes, B. |
Citation: | Journal of Biological Chemistry, 2007; 282(26):18886-18894 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2007 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Carlie Delaine, Clair L. Alvino, Kerrie A. McNeil, Terrance D. Mulhern, Lisbeth Gauguin, Pierre De Meyts, E. Yvonne Jones, James Brown, John C. Wallace, and Briony E. Forbes |
Abstract: | The mammalian insulin-like growth factor (IGF)-II/cation-independent mannose 6-phosphate receptor (IGF2R) binds IGF-II with high affinity. By targeting IGF-II to lysosomal degradation, it plays a role in the maintenance of correct IGF-II levels in the circulation and in target tissues. Loss of IGF2R function is associated with tumor progression; therefore, the IGF2R is often referred to as a tumor suppressor. The interaction between IGF2R and IGF-II involves domains 11 and 13 of the 15 extracellular domains of the receptor. Recently, a hydrophobic binding region was identified on domain 11 of the IGF2R. In contrast, relatively little is known about the residues of IGF-II that are involved in IGF2R binding and the determinants of IGF2R specificity for IGF-II over the structurally related IGF-I. Using a series of novel IGF-II analogues and surface plasmon resonance assays, this study revealed a novel binding surface on IGF-II critical for IGF2R binding. The hydrophobic residues Phe19 and Leu53 are critical for IGF2R binding, as are residues Thr16 and Asp52. Furthermore, Thr16 was identified as playing a major role in determining why IGF-II, but not IGF-I, binds with high affinity to the IGF2R. |
Keywords: | Humans Aspartic Acid Leucine Phenylalanine Threonine Insulin-Like Growth Factor I Insulin-Like Growth Factor II Receptor, IGF Type 2 Circular Dichroism Surface Plasmon Resonance Amino Acid Substitution Mutagenesis, Site-Directed Binding Sites Protein Structure, Quaternary Protein Structure, Tertiary Protein Folding Hydrophobic and Hydrophilic Interactions |
DOI: | 10.1074/jbc.M700531200 |
Published version: | http://dx.doi.org/10.1074/jbc.m700531200 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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