Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function.

Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function.
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DOI:
10.1016/j.tibs.2020.07.008
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发表时间:
2020-12
影响因子:
13.8
通讯作者:
Levitz J
Levitz J
中科院分区:
生物学1区
文献类型:
--
作者:
Ellaithy A;Gonzalez-Maeso J;Logothetis DA;Levitz J

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A类G蛋白偶联受体(GPCR),如视紫红质和β2肾上腺素能受体的开创性结构和光谱研究,提供了跨膜螺旋之间的结构重排如何控制配体结合,受体活化和效应偶联的图片。然而,其他GPCR类的激活机制在很大程度上由于其结构域组装和四级结构的复杂性而仍然更加难以捉摸。在这篇综述中,我们集中在C类GPCR,其中包括代谢型谷氨酸受体(mGluRs)和γ-氨基丁酸B(GABAB)受体最突出。我们讨论了独特的生物物理问题所提出的存在下,大的细胞外配体结合域(LBD)和组成性同源/异源二聚化。此外,我们讨论了最近的研究已经开始解开这些基本的C类GPCR功能如何影响配体结合,受体激活,信号转导,调节辅助蛋白和串扰与其他GPCR的过程。
Groundbreaking structural and spectroscopic studies of class A G protein-coupled receptors (GPCRs), such as rhodopsin and the β2 adrenergic receptor, have provided a picture of how structural rearrangements between transmembrane helices control ligand binding, receptor activation and effector coupling. However, the activation mechanism of other GPCR classes remains more elusive in large part due to complexity in their domain assembly and quaternary structure. In this review, we focus on the class C GPCRs, which includes metabotropic glutamate receptors (mGluRs) and gamma-aminobutyric acid B (GABAB) receptors most prominently. We discuss the unique biophysical questions raised by the presence of large extracellular ligand binding domains (LBD) and constitutive homo/hetero-dimerization. Furthermore, we discuss how recent studies have begun to unravel how these fundamental class C GPCR features impact the processes of ligand binding, receptor activation, signal transduction, regulation by accessory proteins and crosstalk with other GPCRs.
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