Quality control of an integral membrane protein, SecY.

E.coliFtsH是一种膜结合的、依赖于ATP的蛋白酶，其胞浆结构域包括一个AAA家族片段。ATPase的AAA家族成员参与多种细胞过程，包括分泌蛋白的囊泡运输、生物发生细胞器和蛋白质降解。FtsH突变稳定了过量生产的SecY蛋白，该蛋白由于稳定伴侣(SecE)的可用性不足而不稳定。我们发现，另一个完整的膜蛋白F0 ATPase的a亚基也成为FtsH的底物，当它与其他F0亚基结合失败时。快速消除非复杂形式的SecY或亚单位a似乎很重要，因为它们的积累对细胞是有毒的。FtsH似乎构成了膜结合的机制，用于对其他膜蛋白复合体进行质量控制。除了属于蛋白分解功能的表型外，FtsH突变还导致模型膜蛋白(SecY-PhoA)的拓扑结构改变，一些分泌蛋白的转位延迟，以及膜电位的产生缺陷。此外，FtsH突变体的生长缺陷和某些表型可被过量生产的分子伴侣GroE或HtpG所抑制。这些观察表明，FtsH具有伴侣样活性。FtsH可能的伴侣样活性可能对膜蛋白的组装起作用。

E.coli FtsH is a membrane-bound and ATP-dependent protease whose cytosolic domain includes an AAA family segment. Members of the AAA family of ATPase are involved in various cellular processes including vesicular transport of secreted proteins, biogenesis organelles and protein degradation. The ftsH mutations stabilize overproduced SecY protein that was unstable because of the insufficient availability of the stabilizing partner (SecE). We found that another integral membrane protein, subunit a of the F_0 ATPase, became also a substrate of FtsH when it failed to be associated with other F_0 subunits. Rapid elimination of uncomplexed forms of SecY or subunit a seems to be important because their accumulation is toxic to a cell. FtsH seems to constitute membrane-bound machinery for quality control over other membrane protein complexes. In addition to the phenotypes ascribable to the proteolytic function, the ftsH mutations cause altered topology of a model membrane protein (SecY-PhoA), retardation of translocation of some secreted proteins and a defect in generation of membrane potential. In addition, growth defects and some of phenotypes of the ftsH mutants were found to be suppressible by overproduction of molecular chaperones, GroE or HtpG.These observations suggest that FtsH has chaperone-like activities. The possible chaperone-like activity of FtsH may have a role for assembly of membrane proteins.