The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease
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Baker_The CLPS adaptor.pdf
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Author(s)
Hou, Jennifer Y.
Grant, Robert A.
Roman-Hernandez, Giselle
Baker, Tania
Date Issued
July 2011
Journal
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.
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Final published version
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[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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2011.06.009
