The Escherichia coli plasma membrane contains two PHB (prohibitin homology) domain protein complexes of opposite orientations.

Two membrane proteases, FtsH and HtpX, are jointly essential for Escherichia coli cell viability, presumably through their abilities to degrade abnormal membrane proteins. To search for additional cellular factors involved in membrane protein quality control, we isolated multicopy suppressors that alleviated the growth defect of the ftsH/htpX dual disruption mutant. One of them was ybbK, which is renamed qmcA, encoding a membrane-bound prohibitin homology (PHB) domain family protein. Multicopy suppression was also observed with hflK-hflC, encoding another set of PHB domain membrane proteins, which had been known to form a complex (HflKC) and to interact with FtsH. Whereas the DeltaftsH sfhC21 (a viability defect suppressor for DeltaftsH) strain exhibited temperature sensitivity in the presence of cAMP, additional disruption of both qmcA and hflK-hflC exaggerated the growth defect. Pull-down and sedimentation experiments showed that QmcA, like HflKC, forms an oligomer and interacts with FtsH. Protease accessibility assays revealed that QmcA, unlike periplasmically exposed HflKC, possesses a cytoplasmically disposed large C-terminal domain, thus assuming the type I (NOUT-CIN) orientation. We discuss possible significance of having PHB domains on both sides of the membrane.