Academic Journal
Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance
| العنوان: | Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance |
|---|---|
| المؤلفون: | Carrick, F E, Hinds, M G, McNeil, K A, Wallace, J C, Forbes, B E, Norton, R S |
| المصدر: | Journal of Molecular Endocrinology ; volume 34, issue 3, page 685-698 ; ISSN 0952-5041 1479-6813 |
| بيانات النشر: | Bioscientifica |
| سنة النشر: | 2005 |
| الوصف: | 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 15 N- and 2 H/ 15 N-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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.1677/jme.1.01756 |
| الاتاحة: | http://dx.doi.org/10.1677/jme.1.01756 https://jme.bioscientifica.com/view/journals/jme/34/3/0340685.xml https://jme.bioscientifica.com/downloadpdf/journals/jme/34/3/0340685.xml |
| رقم الانضمام: | edsbas.A6837626 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1677/jme.1.01756 |
|---|