Covalent Linkage of Distinct Substrate Degrons Controls Assembly and Disassembly of DegP Proteolytic Cages
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Kim-2011-Covalent Linkage of.pdf
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1.39 MB
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319f56bfb1ca68e9997d17e5e449400a
Author(s)
Kim, Seokhee
Grant, Robert A
Sauer, Robert T
Date Issued
March 2011
Journal
Cell
Publisher
Elsevier
Citation
Kim, Seokhee, Robert A. Grant, and Robert T. Sauer. “Covalent Linkage of Distinct Substrate Degrons Controls Assembly and Disassembly of DegP Proteolytic Cages.” Cell 145, no. 1 (April 2011): 67–78. © 2011 Elsevier Inc.
Version
Final published version
Abstract
Protein quality control requires careful regulation of intracellular proteolysis. For DegP, a periplasmic protease, substrates promote assembly of inactive hexamers into proteolytically active cages with 12, 18, 24, or 30 subunits. Here, we show that sensitive activation and cage assembly require covalent linkage of distinct substrate sequences that affect degradation (degrons). One degron binds the DegP active site, and another degron binds a separate tethering site in PDZ1 in the crystal structure of a substrate-bound DegP dodecamer. FRET experiments demonstrate that active cages assemble rapidly in a reaction that is positively cooperative in substrate concentration, remain stably assembled while uncleaved substrate is present, and dissociate once degradation is complete. Thus, the energy of binding of linked substrate degrons drives assembly of the proteolytic machine responsible for subsequent degradation. Substrate cleavage and depletion results in disassembly, ensuring that DegP is proteolytically active only when sufficient quantities of protein substrates are present.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.02.024
