National Natural Science Foundation of China (NSFC)
31725007,31630087,31800625,21873006,31870835
中国
Other government
2018M631249,2019M650327
引用
ジャーナル: Cell / 年: 2025 タイトル: SecY translocon chaperones protein folding during membrane protein insertion. 著者: Xiaomin Ou / Chengying Ma / Dongjie Sun / Jinkun Xu / Yang Wang / Xiaofei Wu / Dali Wang / Song Yang / Ning Gao / Chen Song / Long Li / 要旨: 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 ...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.