The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease
Author(s)
Hou, Jennifer Y.; Grant, Robert A.; Roman-Hernandez, Giselle; Baker, Tania
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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[subscript 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.
Date issued
2011-07Department
Massachusetts Institute of Technology. Department of BiologyJournal
Molecular Cell
Publisher
Elsevier
Citation
Román-Hernández, Giselle, Jennifer Y. Hou, Robert A. Grant, Robert T. Sauer, and Tania A. Baker. “The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease.” Molecular Cell 43, no. 2 (July 2011): 217-228. Copyright © 2011 Elsevier Inc.
Version: Final published version
ISSN
10972765
1097-4164