The ClpS adaptor mediates staged delivery of N-end rule substrates to the AAA+ ClpAP protease
- PMID: 21777811
- PMCID: PMC3168947
- DOI: 10.1016/j.molcel.2011.06.009
The ClpS adaptor mediates staged delivery of N-end rule substrates to the AAA+ ClpAP protease
Abstract
The ClpS adaptor delivers N-end rule substrates to ClpAP, an energy-dependent AAA+ protease, for degradation. How ClpS binds specific N-end residues is known in atomic detail and clarified here, but the delivery mechanism is poorly understood. We show that substrate binding is enhanced when ClpS binds hexameric ClpA. Reciprocally, N-end rule substrates increase ClpS affinity for ClpA(6). Enhanced binding requires the N-end residue and a peptide bond of the substrate, as well as multiple aspects of ClpS, including a side chain that contacts the substrate α-amino group and the flexible N-terminal extension (NTE). Finally, enhancement also needs the N domain and AAA+ rings of ClpA, connected by a long linker. The NTE can be engaged by the ClpA translocation pore, but ClpS resists unfolding/degradation. We propose a staged-delivery model that illustrates how intimate contacts between the substrate, adaptor, and protease reprogram specificity and coordinate handoff from the adaptor to the protease.
Copyright © 2011 Elsevier Inc. All rights reserved.
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