美国加州理工学院的Rebecca M. Voorhees研究小组近日取得一项新成果。经过不懈努力，他们揭示了人内质网膜蛋白复合物（EMC）插入膜的结构基础。相关论文于2020年5月21日发表在《科学》杂志上。

膜蛋白生物发生中的决定性步骤是将其疏水跨膜螺旋插入脂质双分子层中。 由九个亚基组成的EMC是内质网上保守的共翻译和翻译后插入酶。

研究人员利用冷冻电镜解析了脂质纳米盘中人类EMC的结构，使其整体分辨率达到3.4Å，从而可以建立几乎完整的原子模型。

研究人员依据结构来进行突变，证明底物插入需要富含蛋氨酸的胞质环，并通过由亚基EMC3和EMC6形成的膜内封闭亲水前庭发生。

研究人员猜测EMC使用局部膜薄和带正电的贴片来减少插入脂质双分子层的能量屏障。

附：英文原文

Title: Structural basis for membrane insertion by the human ER membrane protein complex

Author: Tino Pleiner, Giovani Pinton Tomaleri, Kurt Januszyk, Alison J. Inglis, Masami Hazu, Rebecca M. Voorhees

Issue&Volume: 2020/05/21

Abstract: Abstract A defining step in the biogenesis of a membrane protein is the insertion of its hydrophobic transmembrane helices into the lipid bilayer. The nine-subunit ER membrane protein complex (EMC) is a conserved co- and post-translational insertase at the endoplasmic reticulum. We determined the structure of the human EMC in a lipid nanodisc to an overall resolution of 3.4 by cryo-electron microscopy, permitting building of a nearly complete atomic model. We used structure-guided mutagenesis to demonstrate that substrate insertion requires a methionine-rich cytosolic loop and occurs via an enclosed hydrophilic vestibule within the membrane formed by the subunits EMC3 and EMC6. We propose that the EMC uses local membrane thinning and a positively charged patch to decrease the energetic barrier for insertion into the bilayer.

DOI: 10.1126/science.abb5008

Source: https://science.sciencemag.org/content/early/2020/05/20/science.abb5008