Structure of the whole cytosolic region of ATP-dependent protease FtsH
Structure of the whole cytosolic region of ATP-dependent protease FtsH
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DOI：
10.1016/j.molcel.2006.04.020
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发表时间：
2006-06-09
期刊：
影响因子：
16
通讯作者：
Morikawa, Kosuke
中科院分区：
文献类型：
--
作者：
Suno, Ryoji;Niwa, Hajime;Morikawa, Kosuke
一种ATP依赖性蛋白酶FtsH，能抑制膜蛋白的错误组装，以维持膜的完整性，并抑制短寿命的可溶性蛋白，以控制它们的细胞调节。该酶具有N-末端跨膜区段和C-末端胞质区，其由AAA（+）ATP酶结构域和蛋白酶结构域组成。在这里，我们提出了两种晶体结构：蛋白酶结构域和整个胞质区域。胞质区域完全保留ATP依赖性蛋白酶活性，并采用三重对称六聚体结构。蛋白酶结构域显示六重对称性，而AAA（+）结构域，每个含有ADP，交替相对于蛋白酶结构域的两个方向，使“开放”和“封闭”的域间接触。显然，ATP酶仅在封闭形式下有活性，而蛋白酶在开放形式下起作用。蛋白酶催化位点仅可通过从相邻亚基的AAA（+）结构域开始的隧道进入，从而提高了多肽底物通过该隧道易位至蛋白酶位点的可能性。
An ATP-dependent protease, FtsH, digests misassembled membrane proteins in order to maintain membrane integrity and digests short-lived soluble proteins in order to control their cellular regulation. This enzyme has an N-terminal transmembrane segment and a C-terminal cytosolic region consisting of an AAA(+) ATPase domain and a protease domain. Here we present two crystal structures: the protease domain and the whole cytosolic region. The cytosolic region fully retains an ATP-dependent protease activity and adopts a three-fold-symmetric hexameric structure. The protease domains displayed a six-fold symmetry, while the AAA(+) domains, each containing ADP, alternate two orientations relative to the protease domain, making "open" and "closed" interdomain contacts. Apparently, ATPase is active only in the closed form, and protease operates in the open form. The protease catalytic sites are accessible only through a tunnel following from the AAA(+) domain of the adjacent subunit, raising a possibility of translocation of polypeptide substrate to the protease sites through this tunnel.