Ligand binding to the human MT2 melatonin receptor: The role of residues in transmembrane domains 3, 6, and 7

被引:22
作者
Mazna, P
Berka, K
Jelinkova, I
Balik, A
Svoboda, P
Obsilova, V
Obsil, T
Teisinger, J
机构
[1] Acad Sci Czech Republ, Inst Physiol, CR-14220 Prague, Czech Republic
[2] Charles Univ Prague, Fac Sci, Dept Phys & Macromol Chem, Prague 12843, Czech Republic
关键词
MT2 melatonin receptor; site-directed mutagenesis; homolog modeling; G-protein-coupled receptor;
D O I
10.1016/j.bbrc.2005.05.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 H25 may participate in binding of other receptor agonists and/or antagonists. Presented data also hint Lit possible specific interaction between the side-chain of Y188 in second extracellular loop and N-acetyl group of 2-iodomelatonin. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:726 / 734
页数:9
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