FtsH exists as an exceptionally large complex containing HflKC in the plasma membrane of Escherichia coli.

FtsH is an ATP-dependent and membrane-associated protease, which exerts processive proteolysis against membrane-embedded and soluble substrate proteins. Although previous studies suggested that it functions as a homo-oligomer and it also interacts with HflK-HflC membrane protein complex (HflKC), it is still important to address the question of what kind of supramolecular assembly FtsH forms in wild-type cells. Now we show that FtsH in wild-type Escherichia coli cells exists exclusively as a large complex, termed FtsH holo-enzyme, which can be separated from bulk of membrane proteins after detergent solubilization and velocity sedimentation. This complex appears to have molecular mass of around 1000 kDa. A tentative model is presented that it is composed of hexamers of FtsH and of HflKC, with an ability to bind one or a few substrate molecules.