Structure of the Bcs1 AAA-ATPase suggests an airlock-like translocation mechanism for folded proteins
Structure of the Bcs1 AAA-ATPase suggests an airlock-like translocation mechanism for folded proteins
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DOI：
10.1038/s41594-019-0364-1
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发表时间：
2020-01-27
影响因子：
16.8
通讯作者：
Beckmann, Roland
中科院分区：
文献类型：
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作者：
Kater, Lukas;Wagener, Nikola;Beckmann, Roland
有些蛋白质需要完成折叠才能跨膜转运到另一个细胞室。然而，膜的渗透性屏障不应该受到损害，其机制仍然是难以捉摸的。在这里，我们展示了酿酒酵母Bcs1的结构，这是一种线粒体内膜的aaa - atp酶。Bcs1促进Rieske蛋白Rip1的易位，这需要在易位之前折叠并结合2Fe-2S簇，随后整合到bc1复合体中。令人惊讶的是，Bcs1只组装成七聚体的同质低聚物，每个原聚物由一个两性跨膜螺旋、一个中间结构域和一个atp酶结构域组成。它们一起形成两个水前庭，第一个可以从线粒体基质进入，第二个位于内膜中，两者被密封形成的中间区域隔开。基于这种独特的结构，我们提出了一种类似气锁的折叠Rip1易位机制。Bcs1是线粒体内膜上的一种aaa - atp酶，其低温电镜结构揭示了由密封形成的中间结构域分隔的两个大的水前庭，这种结构表明其折叠底物的气锁样易位机制。
Some proteins require completion of folding before translocation across a membrane into another cellular compartment. Yet the permeability barrier of the membrane should not be compromised and mechanisms have remained mostly elusive. Here, we present the structure of Saccharomyces cerevisiae Bcs1, an AAA-ATPase of the inner mitochondrial membrane. Bcs1 facilitates the translocation of the Rieske protein, Rip1, which requires folding and incorporation of a 2Fe-2S cluster before translocation and subsequent integration into the bc1 complex. Surprisingly, Bcs1 assembles into exclusively heptameric homo-oligomers, with each protomer consisting of an amphipathic transmembrane helix, a middle domain and an ATPase domain. Together they form two aqueous vestibules, the first being accessible from the mitochondrial matrix and the second positioned in the inner membrane, with both separated by the seal-forming middle domain. On the basis of this unique architecture, we propose an airlock-like translocation mechanism for folded Rip1.The cryo-EM structure of Bcs1, an AAA-ATPase of the inner mitochondrial membrane, reveals two large aqueous vestibules separated by a seal-forming middle domain, an architecture that suggests an airlock-like translocation mechanism for its folded substrate.