ClpS is an essential component of the N-end rule pathway in Escherichia coli

A. Erbse, R. Schmidt, T. Bornemann, J. Schneider-Mergener, A. Mogk, R. Zahn, D. A. Dougan and B. Bukau ()
Additional contact information
A. Erbse: Universität Heidelberg
R. Schmidt: Universität Heidelberg
T. Bornemann: Universität Heidelberg
J. Schneider-Mergener: Universitätsklinikum Charite, Humboldt-Universität
A. Mogk: Universität Heidelberg
R. Zahn: Universität Heidelberg
D. A. Dougan: Universität Heidelberg
B. Bukau: Universität Heidelberg

Nature, 2006, vol. 439, issue 7077, 753-756

Abstract: Abstract The N-end rule states that the half-life of a protein is determined by the nature of its amino-terminal residue1. Eukaryotes and prokaryotes use N-terminal destabilizing residues as a signal to target proteins for degradation by the N-end rule pathway. In eukaryotes an E3 ligase, N-recognin, recognizes N-end rule substrates and mediates their ubiquitination and degradation by the proteasome1,2. In Escherichia coli, N-end rule substrates are degraded by the AAA + chaperone ClpA in complex with the ClpP peptidase (ClpAP)3. Little is known of the molecular mechanism by which N-end rule substrates are initially selected for proteolysis. Here we report that the ClpAP-specific adaptor, ClpS, is essential for degradation of N-end rule substrates by ClpAP in bacteria. ClpS binds directly to N-terminal destabilizing residues through its substrate-binding site distal to the ClpS–ClpA interface4, and targets these substrates to ClpAP for degradation. Degradation by the N-end rule pathway is more complex than anticipated and several other features are involved, including a net positive charge near the N terminus and an unstructured region between the N-terminal signal and the folded protein substrate. Through interaction with this signal, ClpS converts the ClpAP machine into a protease with exquisitely defined specificity, ideally suited to regulatory proteolysis.

Date: 2006
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DOI: 10.1038/nature04412

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