The molecular architecture of the metalloprotease FtsH
The molecular architecture of the metalloprotease FtsH
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DOI：
10.1073/pnas.0600031103
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发表时间：
2006-02-28
影响因子：
11.1
通讯作者：
Baumann, U
中科院分区：
文献类型：
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作者：
Bieniossek, C;Schalch, T;Baumann, U
ATP依赖性膜蛋白酶FtsH在细菌中是普遍保守的。直向同源物存在于叶绿体和线粒体中，其中在人类中，一个密切的FtsH同源物的丢失会导致一种痉挛性截瘫。FtsH通过降解不需要的或受损的膜蛋白在质量控制中起着至关重要的作用，但它也靶向可溶性信号传导因子，如0，32和β-CII。我们在这里报告的晶体结构的可溶性FtsH的结构，是功能性的酪蛋白溶解和ATIALYSTATE测定。该六聚体分子的分子结构由两个环组成，其中蛋白酶结构域具有全螺旋折叠并形成由AAA结构域构建的环形覆盖的平坦六边形。蛋白酶的活性位点将FtsH分类为Asp-zincin，与以前的报道相反。蛋白酶和AAA环的不同对称性表明靶多肽链进入蛋白水解位点所在的分子内部的可能易位机制。
The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like 0,32 and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATIPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.