DEGRADATION OF CARBOXY-TERMINAL-TAGGED CYTOPLASMIC PROTEINS BY THE ESCHERICHIA-COLI PROTEASE HFLB (FTSH)

Proteins with short nonpolar carboxyl termini are unstable in Escheric hia coli. This proteolytic pathway is used to dispose of polypeptides synthesized from truncated mRNA molecules. Such proteins are tagged wi th an Il-amino-acid nonpolar destabilizing tail via a mechanism involv ing the 10Sa (SsrA) stable RNA and then degraded. We show here that th e ATP-dependent zinc protease HflB (FtsH) is involved in the degradati on of four unstable derivatives of the amino-terminal domain of the la mbda cI repressor: three with nonpolar pentapeptide tails (cI104, cI10 5, cI108) and one with the SsrA tag (cI-SsrA). cI105 and cI-SsrA are a lso degraded by the ClpP-dependent proteases. Loss of ClpP can be comp ensated for by overproducing HflB. In an in vitro system, cI108 and cI -SsrA are degraded by HflB in an energy-dependent reaction, indicating that HflB itself recognizes the carboxyl terminus. These results esta blish a tail-specific pathway for removing abnormal cytoplasmic protei ns via the HflB and Clp proteases.