Membrane driven spatial organization of GPCRs.
Membrane driven spatial organization of GPCRs.
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DOI：
10.1038/srep02909
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发表时间：
2013-10-09
影响因子：
4.6
通讯作者：
Weinstein, Harel
中科院分区：
文献类型：
--
作者：
Mondal, Sayan;Johnston, Jennifer M.;Wang, Hao;Khelashvili, George;Filizola, Marta;Weinstein, Harel
G蛋白偶联受体（GPCR）的空间组织成二聚体和更高级的寡聚体已被证明在体外和体内。药理学读数显示取决于特定的界面，但为什么涉及GPCR结构的特定区域，以及配体决定的状态如何改变它们仍然未知。在这里，我们展示了为什么蛋白质-膜的疏水性匹配是通过对POPC脂质双层中典型β 2-肾上腺素能（β2AR）受体的自发扩散相互作用的粗粒度分子动力学模拟分析在特定界面处寡聚化而实现的。在自发出现的寡聚体阵列中，来自错配的能量惩罚显著降低，使得GPCR的空间组织依赖于单体中的错配模式。与高度同源和结构相似的β 1 AR相比，β 2 AR的这种错配模式非常不同，与实验观察到的β 2 AR和β 1 AR的寡聚化模式一致。这些结果提供了一个低聚反应的结构背景的机械理解。
Spatial organization of G-protein coupled receptors (GPCRs) into dimers and higher order oligomers has been demonstrated in vitro and in vivo. The pharmacological readout was shown to depend on the specific interfaces, but why particular regions of the GPCR structure are involved, and how ligand-determined states change them remains unknown. Here we show why protein-membrane hydrophobic matching is attained upon oligomerization at specific interfaces from an analysis of coarse-grained molecular dynamics simulations of the spontaneous diffusion-interaction of the prototypical beta2-adrenergic (β2AR) receptors in a POPC lipid bilayer. The energy penalty from mismatch is significantly reduced in the spontaneously emerging oligomeric arrays, making the spatial organization of the GPCRs dependent on the pattern of mismatch in the monomer. This mismatch pattern is very different for β2AR compared to the highly homologous and structurally similar β1AR, consonant with experimentally observed oligomerization patterns of β2AR and β1AR. The results provide a mechanistic understanding of the structural context of oligomerization.
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影响因子：
2.9
作者：
Johnston, Jennifer M.;Aburi, Mahalaxmi;Provasi, Davide;Bortolato, Andrea;Urizar, Eneko;Lambert, Nevin A.;Javitch, Jonathan A.;Filizola, Marta
通讯作者：
Filizola, Marta
影响因子：
64.8
作者：
Fotiadis, D;Liang, Y;Palczewski, K
通讯作者：
Palczewski, K
影响因子：
5.5
作者：
de Jong, Djurre H.;Singh, Gurpreet;Marrink, Siewert J.
通讯作者：
Marrink, Siewert J.
影响因子：
3
作者：
EISENHABER, F;LIJNZAAD, P;SCHARF, M
通讯作者：
SCHARF, M
DOI：
10.1073/pnas.0907915107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Hern, Jonathan A.;Baig, Asma H.;Birdsall, Nigel J. M.
通讯作者：
Birdsall, Nigel J. M.