dc.contributor.author | Stinson, Benjamin Michael | |
dc.contributor.author | Baytshtok, Vladimir | |
dc.contributor.author | Schmitz, Karl Robert | |
dc.contributor.author | Baker, Tania | |
dc.contributor.author | Sauer, Robert T. | |
dc.date.accessioned | 2017-05-09T17:38:42Z | |
dc.date.available | 2017-05-09T17:38:42Z | |
dc.date.issued | 2015-04 | |
dc.date.submitted | 2015-01 | |
dc.identifier.issn | 1545-9993 | |
dc.identifier.issn | 1545-9985 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/108783 | |
dc.description.abstract | The hexameric AAA+ ring of Escherichia coli ClpX, an ATP-dependent machine for protein unfolding and translocation, functions with the ClpP peptidase to degrade target substrates. For efficient function, ClpX subunits must switch between nucleotide-loadable (L) and nucleotide-unloadable (U) conformations, but the roles of switching are uncertain. Moreover, it is controversial whether working AAA+-ring enzymes assume symmetric or asymmetric conformations. Here, we show that a covalent ClpX ring with one subunit locked in the U conformation catalyzes robust ATP hydrolysis, with each unlocked subunit able to bind and hydrolyze ATP, albeit with highly asymmetric position-specific affinities. Preventing U↔L interconversion in one subunit alters the cooperativity of ATP hydrolysis and reduces the efficiency of substrate binding, unfolding and degradation, showing that conformational switching enhances multiple aspects of wild-type ClpX function. These results support an asymmetric and probabilistic model of AAA+-ring activity. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant GM-101988) | en_US |
dc.description.sponsorship | Massachusetts Institute of Technology (Poitras Predoctoral Fellowship) | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/nsmb.3012 | en_US |
dc.rights | Article 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.source | PMC | en_US |
dc.title | Subunit asymmetry and roles of conformational switching in the hexameric AAA+ ring of ClpX | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Stinson, Benjamin M et al. “Subunit Asymmetry and Roles of Conformational Switching in the Hexameric AAA+ Ring of ClpX.” Nature Structural & Molecular Biology (2015): n. pag. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Stinson, Benjamin Michael | |
dc.contributor.mitauthor | Baytshtok, Vladimir | |
dc.contributor.mitauthor | Schmitz, Karl Robert | |
dc.contributor.mitauthor | Baker, Tania | |
dc.contributor.mitauthor | Sauer, Robert T. | |
dc.relation.journal | Nature Structural & Molecular Biology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Stinson, Benjamin M; Baytshtok, Vladimir; Schmitz, Karl R; Baker, Tania A; Sauer, Robert T | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-7390-3580 | |
dc.identifier.orcid | https://orcid.org/0000-0002-9309-8662 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1719-5399 | |
dspace.mitauthor.error | true | |
mit.license | PUBLISHER_POLICY | en_US |