研究揭示內質網膜複合物結構

研究揭示內質網膜複合物結構

作者：

小柯機器人

發布時間：2020/6/5 9:26:52

近日，美國Van Andel研究所Huilin Li及其研究團隊報導了內質網膜複合物的結構。2020年6月3日，《自然》在線發表了這一成果。

研究人員首次報導了真核細胞內質網膜複合物（EMC）的冷凍電鏡結構。研究人員發現釀酒酵母EMC包含八個亞基（Emc1-6、Emc7和Emc10），具有較大的管腔區域和較小的胞質區域，並具有由Emc4、Emc5和Emc6以及Emc1和Emc3的跨膜結構域形成的跨膜區域。

研究人員鑑定到以Emc3為中心的5個跨膜螺旋（TMH）摺疊，類似於原核生物的YidC插入酶，並描繪了一個較為親水性的「客戶」蛋白口袋。Emc4的跨膜結構域傾斜遠離EMC的主要跨膜區域，並且可以部分移動。突變研究表明，EMC4的柔韌性和客戶口袋的親水性是EMC功能所必需的。EMC結構揭示了與原核插入酶之間的顯著進化保守性，表明真核TMH插入涉及類似的機制，並為詳細了解眾多真核整合膜蛋白和尾錨蛋白的膜插入提供了框架。

據了解，EMC與Sec61易位子共同將大量多通道整合膜蛋白的TMH插入ER膜中，並且還負責插入一些尾部錨定蛋白。EMC如何實現這一功能尚不清楚。

附：英文原文

Title: Structure of the ER membrane complex, a transmembrane-domain insertase

Author: Lin Bai, Qinglong You, Xiang Feng, Amanda Kovach, Huilin Li

Issue&Volume: 2020-06-03

Abstract: The endoplasmic reticulum (ER) membrane complex (EMC) cooperates with the Sec61 translocon to co-translationally insert a transmembrane helix (TMH) of many multi-pass integral membrane proteins into the ER membrane, and it is also responsible for inserting the TMH of some tail-anchored proteins1,2,3. How EMC accomplishes this feat has been unclear. Here we report the first, to our knowledge, cryo-electron microscopy structure of the eukaryotic EMC. We found that the Saccharomyces cerevisiae EMC contains eight subunits (Emc1–6, Emc7 and Emc10), has a large lumenal region and a smaller cytosolic region, and has a transmembrane region formed by Emc4, Emc5 and Emc6 plus the transmembrane domains of Emc1 and Emc3. We identified a five-TMH fold centred around Emc3 that resembles the prokaryotic YidC insertase and that delineates a largely hydrophilic client protein pocket. The transmembrane domain of Emc4 tilts away from the main transmembrane region of EMC and is partially mobile. Mutational studies demonstrated that the flexibility of Emc4 and the hydrophilicity of the client pocket are required for EMC function. The EMC structure reveals notable evolutionary conservation with the prokaryotic insertases4,5, suggests that eukaryotic TMH insertion involves a similar mechanism, and provides a framework for detailed understanding of membrane insertion for numerous eukaryotic integral membrane proteins and tail-anchored proteins.

DOI: 10.1038/s41586-020-2389-3

Source: https://www.nature.com/articles/s41586-020-2389-3