北京大学李龙研究小组发现在膜蛋白插入过程中，SecY易位伴侣蛋白折叠。该研究于2025年2月19日发表于国际一流学术期刊《细胞》杂志上。

研究人员报道了在原核生物中通过SecY通道（Sec易位）插入的多跨膜蛋白的低温电镜结构。高分辨率结构阐明了大体积氨基酸是如何通过狭窄通道限制的。不同易位状态的比较表明，通道的细胞质腔和细胞外腔分别为促进跨膜段（TMs）的展开和折叠创造了不同的环境。释放的底物TM要么是柔性的，要么是由SecY的TM3和TM4之间意想不到的亲水性凹槽稳定的。沟槽的破坏引起了膜蛋白质组折叠中的全局缺陷。这些发现表明，除了作为被动蛋白质传导通道的作用外，SecY易位还积极充当伴侣，通过多种机制促进膜蛋白的插入和折叠。

研究人员表示，Sec易位对于引导膜蛋白插入脂质双分子层至关重要。膜蛋白的插入和折叠过程尚不清楚。

附：英文原文

Title: SecY translocon chaperones protein folding during membrane protein insertion

Author: Xiaomin Ou, Chengying Ma, Dongjie Sun, Jinkun Xu, Yang Wang, Xiaofei Wu, Dali Wang, Song Yang, Ning Gao, Chen Song, Long Li

Issue&Volume: 2025-02-19

Abstract: The Sec translocon is vital for guiding membrane protein insertion into lipid bilayers. The insertion and folding processes of membrane proteins are poorly understood. Here, we report cryo-electron microscopy structures of multi-spanning membrane proteins inserting through the SecY channel, the Sec translocon in prokaryotes. The high-resolution structures illustrate how bulky amino acids pass the narrow channel restriction. Comparison of different translocation states reveals that the cytoplasmic and extracellular cavities of the channel create distinct environments for promoting the unfolding and folding of transmembrane segments (TMs), respectively. Released substrate TMs are either flexible or stabilized by an unexpected hydrophilic groove between TM3 and TM4 of SecY. Disruption of the groove causes global defects in the folding of the membrane proteome. These findings demonstrate that beyond its role as a passive protein-conducting channel, the SecY translocon actively serves as a chaperone, employing multiple mechanisms to promote membrane protein insertion and folding.

DOI: 10.1016/j.cell.2025.01.037

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00106-0