Misfolded maltose binding protein MalE219 induces the CpxRA envelope stress response by stimulating phosphoryl transfer from CpxA to CpxR

Abstract

In Escherichia coli, the CpxRA sensor regulator system is induced by a variety of signals, including pH, osmolarity, metals and misfolded envelope proteins. Here, we analyzed the effect of the folding defective maltose binding protein MalE219 on the reconstituted Cpx signalling pathway in detail. Surprisingly, autokinase and phosphatase activities of the reconstituted CpxA-6His protein remained unaffected, whereas phosphotransfer to CpxR became activated by MalE219. Since stimulation occurred only in CpxA-containing proteoliposomes, our data provide the first biochemical indication of allosteric stimulation due to direct contact between MalE219 and the sensor kinase CpxA. Consequently, we suggest that this direct interaction is a new mechanism enabling the Cpx pathway to sense misfolded proteins.