title: ClpS is the recognition component for Escherichia coli substrates of the N-end rule degradation pathway.
abstract: The N-end rule degradation pathway states that the half-life of a protein is determined by the nature of its N-terminal residue. In Escherichia coli the adaptor protein ClpS directly interacts with destabilizing N-terminal residues and transfers them to the ClpA/ClpP proteolytic complex for degradation. The crucial role of ClpS in N-end rule degradation is currently under debate, since ClpA/ClpP was shown to process selected N-terminal degrons harbouring destabilizing residues in the absence of ClpS. Here, we investigated the contribution of ClpS to N-end rule degradation by two approaches. First, we performed a systematic mutagenesis of selected N-degron model substrates, demonstrating that ClpS but not ClpA specifically senses the nature of N-terminal residues. Second, we identified two natural N-end rule substrates of E. coli: Dps and PATase (YgjG). The in vivo degradation of both proteins strictly relied on ClpS, thereby establishing the function of ClpS as the essential discriminator of the E. coli N-end rule pathway.
authors.affiliation: Zentrum für Molekulare Biologie Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Schmidt
authors.forename: Regina
authors.initials: R
authors.lastname: Zahn
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
authors.forename: Axel
authors.initials: A
authors.lastname: Mogk