Membrane protein degradation by FtsH can be initiated from either end.
FtsH, a membrane-bound metalloprotease, with cytoplasmic metalloprotease and AAA ATPase domains, degrades both soluble and integral membrane proteins in Escherichia coli. In this paper we investigated how membrane-embedded substrates are recognized by this enzyme. We showed previously that FtsH can initiate processive proteolysis at an N-terminal cytosolic tail of a membrane protein, by recognizing its length (more than 20 amino acid residues) but not exact sequence. Subsequent proteolysis should involve dislocation of the substrates into the cytosol. We now show that this enzyme can also initiate proteolysis at a C-terminal cytosolic tail and that the initiation efficiency depends on the length of the tail. This mode of degradation also appeared to be processive, which can be aborted by a tightly folded periplasmic domain. These results indicate that FtsH can exhibit processivity against membrane-embedded substrates in either the N-to-C or C-to-N direction. Our results also suggest that some membrane proteins receive bidirectional degradation simultaneously. These results raise intriguing questions about the molecular directionality of the dislocation and proteolysis catalyzed by FtsH.
Chiba
Shinobu
S
Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Akiyama
Yoshinori
Y
Ito
Koreaki
K
D049069:ATP-Dependent Proteases; D000469:Alkaline Phosphatase; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D008969:Molecular Sequence Data; D000069816:SEC Translocation Channels
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; C057841:SecY protein, E coli; D018844:Cyclin-Dependent Kinases; D000469:Alkaline Phosphatase; C114089:phoA protein, E coli; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli