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dc.contributor.authorSundar, Shankar
dc.contributor.authorMcGinness, Kathleen E.
dc.contributor.authorBaker, Tania
dc.contributor.authorSauer, Robert T
dc.date.accessioned2015-09-22T19:00:54Z
dc.date.available2015-09-22T19:00:54Z
dc.date.issued2010-09
dc.date.submitted2010-09
dc.identifier.issn00222836
dc.identifier.issn1089-8638
dc.identifier.urihttp://hdl.handle.net/1721.1/98873
dc.description.abstractProteolysis is important for protein quality control and for the proper regulation of many intracellular processes in prokaryotes and eukaryotes. Discerning substrates from other cellular proteins is a key aspect of proteolytic function. The Escherichia coli HslUV protease is a member of a major family of ATP-dependent AAA+ degradation machines. HslU hexamers recognize and unfold native protein substrates and then translocate the polypeptide into the degradation chamber of the HslV peptidase. Although a wealth of structural information is available for this system, relatively little is known about mechanisms of substrate recognition. Here, we demonstrate that mutations in the unstructured N-terminal and C-terminal sequences of two model substrates alter HslUV recognition and degradation kinetics, including changes in V[subscript max]. By introducing N- or C-terminal sequences that serve as recognition sites for specific peptide-binding proteins, we show that blocking either terminus of the substrate interferes with HslUV degradation, with synergistic effects when both termini are obstructed. These results support a model in which one terminus of the substrate is tethered to the protease and the other terminus is engaged by the translocation/unfolding machinery in the HslU pore. Thus, degradation appears to consist of discrete steps, which involve the interaction of different terminal sequence signals in the substrate with different receptor sites in the HslUV protease.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant AI-16892)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.jmb.2010.09.008en_US
dc.rightsCreative Commons Attribution-Noncommercial-NoDerivativesen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleMultiple Sequence Signals Direct Recognition and Degradation of Protein Substrates by the AAA+ Protease HslUVen_US
dc.typeArticleen_US
dc.identifier.citationSundar, Shankar, Kathleen E. McGinness, Tania A. Baker, and Robert T. Sauer. “Multiple Sequence Signals Direct Recognition and Degradation of Protein Substrates by the AAA+ Protease HslUV.” Journal of Molecular Biology 403, no. 3 (October 2010): 420–429.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorSundar, Shankaren_US
dc.contributor.mitauthorMcGinness, Kathleen E.en_US
dc.contributor.mitauthorBaker, Taniaen_US
dc.contributor.mitauthorSauer, Robert T.en_US
dc.relation.journalJournal of Molecular Biologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSundar, Shankar; McGinness, Kathleen E.; Baker, Tania A.; Sauer, Robert T.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-1719-5399
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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