Control of extracytoplasmic stress responses by regulated intramembrane proteolysis

大肠杆菌σ^E被胞外应激诱导的抗σ^E蛋白rseA(一种II型单跨膜蛋白)的两步裂解激活。我们发现RseP(前身为YEL)是真核细胞中S2P蛋白酶的同源物，它的功能是一种“调节的膜内蛋白分解”(RIP)酶，它在DEGS对周质侧作第一次切割之后，引入第二次“膜内”裂解为抗σ^E蛋白(RseA)。我们的体内和体外结果表明，RseP直接催化RseA跨膜序列中的蛋白降解。我们还发现，RseP可以切割一些与RseA无关的模型膜蛋白的跨膜序列，前提是跨膜区含有低螺旋倾向的残基。我们现在正在利用由纯化的组分重组的体外反应系统来研究RseA的两步蛋白降解的分子机制及其调控。

E.coli σ^E is activated by extracytoplasmic stress-induced two step cleavages of the anti-σ^E protein, RseA (a type II single-spanning membrane protein). We showed that RseP (formerly YaeL), an E.coli homolog of the eukaryotic S2P protease, functions as a "RIP(regulated intramembrane proteolysis)" protease that introduces the second "intramembrane" cleavage into anti-σ^E protein (RseA) following the first cleavage on the periplasmic side by DegS. Our in vivo and in vitro results demonstrated that RseP directly catalyzes proteolysis within the transmembrane sequence of RseA. We also found that RseP can cleave transmembrane sequences of some model membrane proteins that are unrelated to RseA, provided that the transmembrane region contains residues of low helical propensity. We are now addressing the molecular mechanisms of the two-step proteolysis of RseA and its regulation using in vitro reaction system reconstituted from purified components.