DOI：10.1038/nature17163 作者：Tom A. Rapoport
摘要 : 细菌的 “总分泌” (Sec)通道 (该通道依赖于SecY蛋白转位通道)负责穿过细菌细胞膜运输蛋白。
细菌的 “总分泌” (Sec)通道 (该通道依赖于SecY蛋白转位通道)负责穿过细菌细胞膜运输蛋白。蛋白向该通道中插入的机制因没有处于活性状态的该通道的高分辨率结构而一直不清楚。Tom Rapoport 及同事报告了一个与基质相结合的SecY通道和SecA ATPase的晶体结构，这为了解细菌的翻译后转位过程提供了重要的分子信息。
Hydrophobic signal sequences target secretory polypeptides to a protein-conducting channel formed by a heterotrimeric membrane protein complex, the prokaryotic SecY or eukaryotic Sec61 complex. How signal sequences are recognized is poorly understood, particularly because they are diverse in sequence and length. Structures of the inactive channel show that the largest subunit, SecY or Sec61α, consists of two halves that form an hourglass-shaped pore with a constriction in the middle of the membrane and a lateral gate that faces lipid. The cytoplasmic funnel is empty, while the extracellular funnel is filled with a plug domain. In bacteria, the SecY channel associates with the translating ribosome in co-translational translocation, and with the SecA ATPase in post-translational translocation. How a translocating polypeptide inserts into the channel is uncertain, as cryo-electron microscopy structures of the active channel have a relatively low resolution (~10 Å) or are of insufficient quality. Here we report a crystal structure of the active channel, assembled from SecY complex, the SecA ATPase, and a segment of a secretory protein fused into SecA. The translocating protein segment inserts into the channel as a loop, displacing the plug domain. The hydrophobic core of the signal sequence forms a helix that sits in a groove outside the lateral gate, while the following polypeptide segment intercalates into the gate. The carboxy (C)-terminal section of the polypeptide loop is located in the channel, surrounded by residues of the pore ring. Thus, during translocation, the hydrophobic segments of signal sequences, and probably bilayer-spanning domains of nascent membrane proteins, exit the lateral gate and dock at a specific site that faces the lipid phase.
来源： Nature 浏览次数：0