Translocation Mechanism of Allosteric Sodium Ions in β2-Adrenoceptor,Journal of Chemical Information and Modeling

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Translocation Mechanism of Allosteric Sodium Ions in β2-Adrenoceptor
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2022-06-13 , DOI: 10.1021/acs.jcim.2c00170
Xueying Wang ₁ , Shuguang Yuan _{1,

2} , H C Stephen Chan ₁

Affiliation

The allosteric modulation of G-protein-coupled receptors (GPCRs) by sodium ions has received significant attention as the crystal structures of several receptors show the binding of sodium ions (Na⁺) at the conserved D^2.50. Theoretical studies have shown that extracellular Na⁺ would enter the allosteric D^2.50 via the orthosteric site. However, it remains unclear how the bound allosteric Na⁺ would leave the GPCRs. In this study, we performed molecular dynamics (MD) simulations to illustrate the energy barriers of Na⁺ transfer through the transmembrane helix bundle of β₂AR. In contrast to the postulations from other GPCRs, the translocation of this allosteric Na⁺ into the intracellular side is found to be significantly difficult. Hence, the translocation direction could be receptor-specific.

中文翻译：

β2-肾上腺素受体变构钠离子的易位机制

钠离子对 G 蛋白偶联受体 (GPCR) 的变构调节受到了极大的关注，因为几种受体的晶体结构显示钠离子 (Na ⁺ ) 在保守的 D ^2.50处结合。理论研究表明，细胞外Na ⁺会通过正构位点进入变构D ^2.50。然而，仍不清楚结合的变构 Na ⁺将如何离开 GPCR。在这项研究中，我们进行了分子动力学 (MD) 模拟，以说明 Na ⁺通过 β _{2的跨膜螺旋束转移的能垒}增强现实。与其他 GPCR 的假设相反，发现这种变构 Na ⁺易位到细胞内侧非常困难。因此，易位方向可能是受体特异性的。

更新日期：2022-06-13

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