Bieniossek Christoph, Schalch Thomas, Bumann Mario, Meister Markus, Meier Reto, Baumann Ulrich
Departement für Chemie und Biochemie, Universität Bern, Switzerland.
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3066-71. doi: 10.1073/pnas.0600031103. Epub 2006 Feb 16.
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 sigma(32) and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase 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.
依赖ATP的整合膜蛋白酶FtsH在细菌中普遍保守。其直系同源物存在于叶绿体和线粒体中，而在人类中，一种与之密切相关的FtsH同源物的缺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发挥关键作用，但它也靶向可溶性信号因子，如sigma(32)和lambda-CII。我们在此报告一种可溶性FtsH构建体的晶体结构，该构建体在酪蛋白水解和ATP酶测定中具有功能。这个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一个扁平的六边形，该六边形被由AAA结构域构建的环形结构覆盖。与之前的报道相反，蛋白酶的活性位点将FtsH归类为天冬氨酸锌蛋白酶。蛋白酶环和AAA环的不同对称性表明目标多肽链可能向分子内部（即蛋白水解位点所在处）的转运机制。
