韩国国立首尔大学Tae-Young Yoo、Hee-Jung Choi和美国加州大学洛杉矶分校James U. Bowie等研究人员合作，通过直接观察螺旋膜蛋白折叠揭示了一个通用的N到C端蛋白折叠模式。该研究于2019年11月29日发表于国际一流学术期刊《科学》。

研究人员描述了一种单分子力显微镜技术，其可监测囊泡和双层膜环境中螺旋膜蛋白的折叠。在高强度下完全解开蛋白质后，研究人员降低了用力从而启动折叠，同时跨膜螺旋以Z字形方式排列在双层中，从而对折叠施加了最小限度的约束。

研究人员使用该方法来表征了大肠杆菌菱形蛋白酶GlpG和人β2-肾上腺素能受体的折叠途径。尽管它们在进化上相距甚远，但两种蛋白质均以严格的N到C末端方式折叠，并以螺旋发夹为单位累积结构。这些共同特征表明，完整的螺旋膜蛋白已经进化到可以通过共翻译折叠来最大化其适应性。

据悉，想要了解膜蛋白的生物发生，我们需要探索双层膜环境中的折叠。

附：英文原文

Title: Watching helical membrane proteins fold reveals a common N-to-C-terminal folding pathway

Author: Hyun-Kyu Choi, Duyoung Min, Hyunook Kang, Min Ju Shon, Sang-Hyun Rah, Hak Chan Kim, Hawoong Jeong, Hee-Jung Choi, James U. Bowie, Tae-Young Yoon

Issue&Volume: 2019/11/29

Abstract: To understand membrane protein biogenesis, we need to explore folding within a bilayer context. Here, we describe a single-molecule force microscopy technique that monitors the folding of helical membrane proteins in vesicle and bicelle environments. After completely unfolding the protein at high force, we lower the force to initiate folding while transmembrane helices are aligned in a zigzag manner within the bilayer, thereby imposing minimal constraints on folding. We used the approach to characterize the folding pathways of the Escherichia coli rhomboid protease GlpG and the human β2-adrenergic receptor. Despite their evolutionary distance, both proteins fold in a strict N-to-C-terminal fashion, accruing structures in units of helical hairpins. These common features suggest that integral helical membrane proteins have evolved to maximize their fitness with cotranslational folding.

DOI: 10.1126/science.aaw8208

Source: https://science.sciencemag.org/content/366/6469/1150