Laboratory of Biomolecular Research, Paul Scherrer Institut, Förschunggstrasse 111, 5232 Villigen, Switzerland.
Laboratory of Biomolecular Research, Paul Scherrer Institut, Förschunggstrasse 111, 5232 Villigen, Switzerland; Department of Biology, ETH Zürich, Wolfgang-Pauli-Strasse 27, Zürich 8093, Switzerland.
J Struct Biol. 2021 Jun;213(2):107699. doi: 10.1016/j.jsb.2021.107699. Epub 2021 Feb 3.
G-protein coupled receptors (GPCRs) are among the most versatile signal transducers in the cell. Once activated, GPCRs sample a large conformational space and couple to G-proteins to initiate distinct signaling pathways. The dynamical behavior of GPCR-G-protein complexes is difficult characterize structurally, and it might hinder obtaining routine high-resolution density maps in single-particle reconstructions. Here, we used variability analysis on the rhodopsin-G-Fab16 complex cryo-EM dataset, and the results provide insights into the dynamic nature of the receptor-complex interaction. We compare the outcome of this analysis with recent results obtained on the cannabinoid-G- and secretin-G-receptor complexes. Despite differences related to the biochemical compositions of the three samples, a set of consensus movements emerges. We anticipate that systematic variability analysis on GPCR-G-protein complexes may provide useful information not only at the biological level, but also for improving the preparation of more stable samples for cryo-EM single-particle analysis.
G 蛋白偶联受体 (GPCRs) 是细胞中用途最广泛的信号转导分子之一。一旦被激活，GPCR 会采样大量构象空间，并与 G 蛋白偶联，从而启动不同的信号通路。GPCR-G 蛋白复合物的动力学行为在结构上很难描述，这可能会阻碍在单颗粒重建中获得常规的高分辨率密度图。在这里，我们使用变异性分析对视紫红质-G-Fab16 复合物冷冻电镜数据集进行了分析，结果为受体-复合物相互作用的动态性质提供了深入了解。我们将该分析的结果与最近在大麻素-G-和分泌素-G-受体复合物上获得的结果进行了比较。尽管与三种样品的生化组成有关，但出现了一组共识运动。我们预计，对 GPCR-G 蛋白复合物进行系统的变异性分析不仅可以提供生物学水平上的有用信息，还可以改善更稳定的冷冻电镜单颗粒分析样品的制备。
