Li Weikai, Schulman Sol, Boyd Dana, Erlandson Karl, Beckwith Jon, Rapoport Tom A
Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Mol Cell. 2007 May 25;26(4):511-21. doi: 10.1016/j.molcel.2007.05.002.
Proteins are translocated across membranes through a channel that is formed by the prokaryotic SecY or eukaryotic Sec61 complex. The crystal structure of the SecY channel from M. jannaschii revealed a plug domain that appears to seal the channel in its closed state. However, the role of the plug remains unclear, particularly because plug deletion mutants in S. cerevisiae are functional. Here, we demonstrate that plug deletion mutants in E. coli SecY are also functional and even efficiently translocate proteins with defective or missing signal sequences. The crystal structures of equivalent plug deletions in SecY of M. jannaschii show that, although the overall structures are maintained, new plugs are formed. These lack many interactions that normally stabilize the closed channel, explaining why the channels can open for proteins with signal-sequence mutations. Our data show that the plug domain is required to maintain a closed state of the channel and suggest a mechanism for channel gating.
蛋白质通过由原核生物SecY或真核生物Sec61复合物形成的通道跨膜转运。詹氏甲烷球菌SecY通道的晶体结构显示，有一个塞子结构域，在通道处于关闭状态时似乎能封闭通道。然而，塞子的作用仍不清楚，特别是因为酿酒酵母中的塞子缺失突变体仍具有功能。在这里，我们证明大肠杆菌SecY中的塞子缺失突变体也具有功能，甚至能有效地转运信号序列有缺陷或缺失的蛋白质。詹氏甲烷球菌SecY中同等塞子缺失的晶体结构表明，虽然整体结构得以维持，但会形成新的塞子。这些新塞子缺乏许多通常能稳定关闭通道的相互作用，这就解释了为什么通道能够为信号序列发生突变的蛋白质打开。我们的数据表明，塞子结构域是维持通道关闭状态所必需的，并提出了一种通道门控机制。
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