Structural insights into the G protein selectivity revealed by the human EP3-Gi signaling complex
Structural insights into the G protein selectivity revealed by the human EP3-Gi signaling complex
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人类 EP3-Gi 信号复合物揭示的 G 蛋白选择性的结构见解
DOI：
10.1016/j.celrep.2022.111323
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Takuya Kobayashi
中科院分区：
文献类型：
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作者：
Ryoji Suno;Yukihiko Sugita;Kazushi Morimoto;Hiroko Takazaki;Hirokazu Tsujimoto;Mika Hirose;Chiyo Suno-Ikeda;Norimichi Nomura;Tomoya Hino;Asuka Inoue;Kenji Iwasaki;Takayuki Kato;So Iwata;Takuya Kobayashi
前列腺素受体涉及广泛的功能，包括炎症、免疫反应、生殖和癌症。我们的团队之前已经确定了活性样EP3与其内源性激动剂前列腺素E2结合的晶体结构。在这里，我们展示了人类ep3 - gissignaling复合物的单粒子冷冻电镜（cryo-EM）结构，分辨率为3.4 Å。该结构揭示了Gito EP3的结合模式以及Gito结合引起的EP3结构变化。此外，我们比较了ep3 - giccomplexes的结构与其他类型的前列腺素受体（EP2和EP4）结合的gs，并检查在受体- g蛋白界面氨基酸组成的差异。突变分析表明，G蛋白的选择性取决于第二胞内环和TM5中的特定氨基酸残基。
Prostaglandin receptors have been implicated in a wide range of functions, including inflammation, immune response, reproduction, and cancer. Our group has previously determined the crystal structure of the active-like EP3 bound to its endogenous agonist, prostaglandin E2. Here, we present the single-particle cryoelectron microscopy (cryo-EM) structure of the human EP3-Gisignaling complex at a resolution of 3.4 Å. The structure reveals the binding mode of Gito EP3 and the structural changes induced in EP3 by Gibinding. In addition, we compare the structure of the EP3-Gicomplex with other subtypes of prostaglandin receptors (EP2 and EP4) bound to Gsthat have been previously reported and examine the differences in amino acid composition at the receptor-G protein interface. Mutational analysis reveals that the selectivity of the G protein depends on specific amino acid residues in the second intracellular loop and TM5.