| Autor: |
Mann R; Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK., Nasr N, Hadden D, Sinfield J, Abidi F, Al-Sabah S, de Maturana RL, Treece-Birch J, Willshaw A, Donnelly D |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical Society transactions [Biochem Soc Trans] 2007 Aug; Vol. 35 (Pt 4), pp. 713-6. |
| DOI: |
10.1042/BST0350713 |
| Abstrakt: |
The receptor for GLP-1 [glucagon-like peptide-1-(7-36)-amide] is a member of the 'Family B' of GPCRs (G-protein-coupled receptors) comprising an extracellular N-terminal domain containing six conserved cysteine residues (the N-domain) and a core domain (or J-domain) comprising the seven transmembrane helices and interconnecting loop regions. According to the two-domain model for peptide binding, the N-domain is primarily responsible for providing most of the peptide binding energy, whereas the core domain is responsible for binding the N-terminal region of the peptide agonists and transmitting the signal to the intracellular G-protein. Two interesting differences between the binding properties of two GLP-1 receptor agonists, GLP-1 and EX-4 (exendin-4), can be observed. First, while GLP-1 requires its full length to maintain high affinity, the eight N-terminal residues of EX-4 can be removed with little reduction in affinity. Secondly, EX-4 (but not GLP-1) can bind to the fully isolated N-domain of the receptor with an affinity matching that of the full-length receptor. In order to better understand these differences, we have studied the interaction between combinations of full-length or truncated ligands with full-length or truncated receptors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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