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dc.contributor.authorHou, Jennifer Y.
dc.contributor.authorGrant, Robert A.
dc.contributor.authorRoman-Hernandez, Giselle
dc.contributor.authorBaker, Tania
dc.date.accessioned2014-01-27T16:21:55Z
dc.date.available2014-01-27T16:21:55Z
dc.date.issued2011-07
dc.date.submitted2011-04
dc.identifier.issn10972765
dc.identifier.issn1097-4164
dc.identifier.urihttp://hdl.handle.net/1721.1/84568
dc.description.abstractThe 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.en_US
dc.description.sponsorshipHoward Hughes Medical Instituteen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant AI-15706)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant AI-16892)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM-049224)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.molcel.2011.06.009en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevier Open Archiveen_US
dc.titleThe ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Proteaseen_US
dc.typeArticleen_US
dc.identifier.citationRomán-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.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorRoman-Hernandez, Giselleen_US
dc.contributor.mitauthorHou, Jennifer Y.en_US
dc.contributor.mitauthorGrant, Robert A.en_US
dc.contributor.mitauthorSauer, Robert T.en_US
dc.contributor.mitauthorBaker, Taniaen_US
dc.relation.journalMolecular Cellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsRomán-Hernández, Giselle; Hou, Jennifer Y.; Grant, Robert A.; Sauer, Robert T.; Baker, Tania A.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-1719-5399
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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