Quality control of an integral membrane protein, SecY.

大肠杆菌FtsH是一种膜结合和atp依赖的蛋白酶，其胞质结构域包括一个AAA家族片段。atp酶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突变稳定了过量产生的SecY蛋白，这种蛋白由于稳定伴侣（SecE）的可用性不足而不稳定。我们发现另一个完整的膜蛋白，F_0 atp酶的亚基a，当它不能与其他F_0亚基结合时，也成为FtsH的底物。快速清除非复杂形式的SecY或亚基a似乎很重要，因为它们的积累对细胞是有毒的。与其他膜蛋白复合物相比，FtsH似乎构成了质量控制的膜结合机制。除了可归因于蛋白水解功能的表型外，ftsH突变还导致模型膜蛋白（SecY-PhoA）的拓扑结构改变，一些分泌蛋白的易位延迟以及膜电位的产生缺陷。此外，发现ftsH突变体的生长缺陷和某些表型可以通过过量产生分子伴侣、GroE或HtpG来抑制。这些观察结果表明，FtsH具有类似伴侣的活性。FtsH可能具有伴侣样活性，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.