近日，美国Van Andel研究所Huilin Li及其研究团队报道了内质网膜复合物的结构。2020年6月3日，《自然》在线发表了这一成果。
研究人员首次报道了真核细胞内质网膜复合物（EMC）的冷冻电镜结构。研究人员发现酿酒酵母EMC包含八个亚基（Emc1-6、Emc7和Emc10），具有较大的管腔区域和较小的胞质区域，并具有由Emc4、Emc5和Emc6以及Emc1和Emc3的跨膜结构域形成的跨膜区域。
研究人员鉴定到以Emc3为中心的5个跨膜螺旋（TMH）折叠，类似于原核生物的YidC插入酶，并描绘了一个较为亲水性的“客户”蛋白口袋。Emc4的跨膜结构域倾斜远离EMC的主要跨膜区域，并且可以部分移动。突变研究表明，EMC4的柔韧性和客户口袋的亲水性是EMC功能所必需的。EMC结构揭示了与原核插入酶之间的显著进化保守性，表明真核TMH插入涉及类似的机制，并为详细了解众多真核整合膜蛋白和尾锚蛋白的膜插入提供了框架。
据了解，EMC与Sec61易位子共同将大量多通道整合膜蛋白的TMH插入ER膜中，并且还负责插入一些尾部锚定蛋白。EMC如何实现这一功能尚不清楚。
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
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
