Differences in conformational properties of the second intracellular loop (IL2) in 5HT(2C) receptors modified by RNA editing can account for G protein coupling efficiency.
Differences in conformational properties of the second intracellular loop (IL2) in 5HT(2C) receptors modified by RNA editing can account for G protein coupling efficiency.
复制标题
通过 RNA 编辑修饰的 5HT(2C) 受体中第二个细胞内环 (IL2) 构象特性的差异可以解释 G 蛋白偶联效率。
DOI：
10.1093/protein/14.6.409
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Weinstein,H
中科院分区：
文献类型：
--
作者：
Visiers,I;Hassan,SA;Weinstein,H
Adenosine-to-inosine RNA editing events that have been demonstrated for 5HT2Creceptors resulted in alterations of the amino acid sequence at positions 156, 158 and 160 in the intracellular loop 2 (IL2) region. The edited receptor isoforms were shown to have reduced basal activity, but similar maximum responses to agonist binding. To identify the molecular mechanism of these pharmacological effects of editing we explored the conformational properties of the edited IL2 in comparison with the wild type. The results from conformational studies of the IL2 isoforms, using biased Monte Carlo simulations with an implicit solvent model based on a screened Coulomb potential, show that the compared loops differ in their preferred spatial orientations as a result of differences in the conformational space that is accessible to them by energy criteria. For the IL2 of the unedited (5HT2C-INI) receptor, the preference for structures oriented towards the 7TM bundle is larger than for the 5HT2C-VGVedited receptor. This difference in preferred orientation can affect the association of IL2 with other intracellular loop domains involved in G protein coupling and hence the coupling efficiency. The results illustrate the high sensitivity of the system to small changes in the interaction surface presented to other intracellular loops, and/or the G protein.
