Ligand binding to the human MT2 melatonin receptor: The role of residues in transmembrane domains 3, 6, and 7
- Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague (Czech Republic)
- Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 2030/8, 128 43 Prague (Czech Republic)
To better understand the mechanism of interactions between G-protein-coupled melatonin receptors and their ligands, our previously reported homology model of human MT2 receptor with docked 2-iodomelatonin was further refined and used to select residues within TM3, TM6, and TM7 potentially important for receptor-ligand interactions. Selected residues were mutated and radioligand-binding assay was used to test the binding affinities of hMT2 receptors transiently expressed in HEK293 cells. Our data demonstrate that residues N268 and A275 in TM6 as well as residues V291 and L295 in TM7 are essential for 2-iodomelatonin binding to the hMT2 receptor, while TM3 residues M120, G121, V124, and I125 may participate in binding of other receptor agonists and/or antagonists. Presented data also hint at possible specific interaction between the side-chain of Y188 in second extracellular loop and N-acetyl group of 2-iodomelatonin.
- OSTI ID:
- 20710843
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 332, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2005.05.017; PII: S0006-291X(05)00968-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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