Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/27518
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance |
Author: | Carrick, F. Hinds, M. McNeil, K. Wallace, J. Forbes, B. Norton, R. |
Citation: | Journal of Molecular Endocrinology, 2005; 34(3):685-698 |
Publisher: | Soc Endocrinology |
Issue Date: | 2005 |
ISSN: | 0952-5041 1479-6813 |
Statement of Responsibility: | F.E. Carrick, M.G. Hinds, K.A. McNeil, J.C. Wallace, B.E. Forbes and R.S. Norton |
Abstract: | The interaction of IGF binding protein-2 (IGFBP-2) with IGF-I and -II has been investigated in solution using nuclear magnetic resonance (NMR) spectroscopy. Chemical shift perturbations in 15N- and 2H/15N-labelled IGF-I or -II upon binding to unlabelled thioredoxin-tagged bovine IGFBP-2 (Trx(1-279)IGFBP-2) have been monitored to identify residues involved directly in the binding interaction as well as any affected by conformational changes associated with the interaction. A key step in obtaining high-quality spectra of the complexes was the use of transverse relaxation optimised spectroscopy (TROSY) methods with partially deuterated ligands. Indeed, because the effects of conformational averaging and aggregation are eliminated in IGF-I and -II bound to IGFBP-2, the spectra of the complexes are actually superior to those of the free ligands. Comparison of our results with the crystal structure of the complex between IGF-I and an N-terminal fragment of IGFBP-5 allowed identification of those residues perturbed by the C-domain of IGFBP-2. Other perturbations, such as those of Gly 19 and Asp 20 of IGF-I (and the corresponding residues in IGF-II) - which are located in a reverse turn linking N-domain and C-domain interactive surfaces - are due to local conformational changes in the IGF-I and -II. Our results confirm that the C-domain of IGFBP-2 plays a key role in binding regions of IGF-I and -II that are also involved in binding to the type-1 IGF receptor and thereby blocking ligand binding to this receptor. |
Keywords: | Humans Insulin-Like Growth Factor I Insulin-Like Growth Factor II Insulin-Like Growth Factor Binding Protein 2 Recombinant Proteins Chromatography, Gel Nuclear Magnetic Resonance, Biomolecular Binding Sites Amino Acid Sequence Protein Binding Sequence Homology, Amino Acid Molecular Sequence Data |
Rights: | © 2005 Society for Endocrinology |
DOI: | 10.1677/jme.1.01756 |
Published version: | http://dx.doi.org/10.1677/jme.1.01756 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.