A Global Map of G Protein Signaling Regulation by RGS Proteins.
A Global Map of G Protein Signaling Regulation by RGS Proteins.
复制标题
DOI：
10.1016/j.cell.2020.08.052
复制
发表时间：
2020-10-15
期刊：
影响因子：
64.5
通讯作者：
Martemyanov KA
中科院分区：
文献类型：
--
作者：
Masuho I;Balaji S;Muntean BS;Skamangas NK;Chavali S;Tesmer JJG;Babu MM;Martemyanov KA
G蛋白信号传导的程度和时间的控制由G蛋白信号传导调节器（Regulator of G protein Signaling，RGS）蛋白提供，其使G蛋白α亚基（Gα）失活。哺乳动物基因组编码20个典型的RGS和16个Gα基因，在生理和疾病中发挥关键作用。为了理解RGS对Gα调节的选择性原则，我们使用活细胞中的实时动力学测量来检查所有典型的人类RGS蛋白的催化活性及其对一整套Gα底物的选择性。这些数据揭示了控制RGS-Gα识别的规则，其选择性的结构基础，并提供了具有确定选择性的工程RGS蛋白的原则。该研究还探索了通过祖先重建的RGS-Gα选择性的演变，并演示了RGS中天然存在的非同义变体如何改变信号传导。这些结果为解码信号选择性提供了蓝图，并推进了我们对分子识别原理的理解。Masuho等人定量地定义了G蛋白信号传导调节因子（Regulator of G protein Signaling，RGS）家族所有典型成员的G蛋白选择性。基于这些信息，他们确定了选择性RGS-G蛋白识别的结构基础，并展示了选择性决定簇是如何进化的。他们进一步表明，RGS-G蛋白的选择性受到突变基因组景观的影响，并且可以合理地改变。
The control over the extent and timing of G protein signaling is provided by the Regulator of G protein Signaling (RGS) proteins that deactivate G protein α subunits (Gα). Mammalian genomes encode 20 canonical RGS and 16 Gα genes with key roles in physiology and disease. To understand principles governing selectivity of Gα regulation by RGS, we examine the catalytic activity of all canonical human RGS proteins and their selectivity for a complete set of Gα substrates using real-time kinetic measurements in living cells. The data reveal rules governing RGS-Gα recognition, the structural basis of its selectivity, and provide principles for engineering RGS proteins with defined selectivity. The study also explores the evolution of RGS-Gα selectivity through ancestral reconstruction and demonstrates how naturally-occurring non-synonymous variants in RGS alter signaling. These results provide a blueprint for decoding signaling selectivity and advance our understanding of molecular recognition principles. Masuho et al. quantitatively define G protein selectivity of all canonical members of the Regulator of G protein Signaling (RGS) family. Based on this information, they determine the structural basis of selective RGS-G protein recognition and demonstrate how selectivity determinants evolved. They further showed that the RGS-G protein selectivity is impacted by the mutational genomic landscape and can be rationally altered.
登录
查看更多内容
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
7.3
作者：
DiGiacomo, Vincent;Maziarz, Marcin;Garcia-Marcos, Mikel
通讯作者：
Garcia-Marcos, Mikel
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
16.6
作者：
Doi, Masao;Ishida, Atsushi;Miyake, Akiko;Sato, Miho;Komatsu, Rie;Yamazaki, Fumiyoshi;Kimura, Ikuo;Tsuchiya, Soken;Kori, Hiroshi;Seo, Kazuyuki;Yamaguchi, Yoshiaki;Matsuo, Masahiro;Fustin, Jean-Michel;Tanaka, Rina;Santo, Yasuko;Yamada, Hiroyuki;Takahashi, Yukari;Araki, Michihiro;Nakao, Kazuki;Aizawa, Shinichi;Kobayashi, Masaki;Obrietan, Karl;Tsujimoto, Gozoh;Okamura, Hitoshi
通讯作者：
Okamura, Hitoshi
影响因子：
4.8
作者：
Chatterjee, TK;Liu, ZY;Fisher, RA
通讯作者：
Fisher, RA