dc.contributor.author | Stein, Benjamin Joseph | |
dc.contributor.author | Grant, Robert A. | |
dc.contributor.author | Sauer, Robert T. | |
dc.contributor.author | Baker, Tania | |
dc.date.accessioned | 2018-06-06T18:35:31Z | |
dc.date.available | 2018-06-06T18:35:31Z | |
dc.date.issued | 2016-01 | |
dc.date.submitted | 2015-12 | |
dc.identifier.issn | 0969-2126 | |
dc.identifier.issn | 1878-4186 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/116152 | |
dc.description.abstract | The N-end rule dictates that a protein's N-terminal residue determines its half-life. In bacteria, the ClpS adaptor mediates N-end-rule degradation, by recognizing proteins bearing specific N-terminal residues and delivering them to the ClpAP AAA+ protease. Unlike most bacterial clades, many α-proteobacteria encode two ClpS paralogs, ClpS1 and ClpS2. Here, we demonstrate that both ClpS1 and ClpS2 from A. tumefaciens deliver N-end-rule substrates to ClpA, but ClpS2 has more stringent binding specificity, recognizing only a subset of the canonical bacterial N-end-rule residues. The basis of this enhanced specificity is addressed by crystal structures of ClpS2, with and without ligand, and structure-guided mutagenesis, revealing protein conformational changes and remodeling in the substrate-binding pocket. We find that ClpS1 and ClpS2 are differentially expressed during growth in A. tumefaciens and conclude that the use of multiple ClpS paralogs allows fine-tuning of N-end-rule degradation at the level of substrate recognition. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant T32GM007287) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant GM-49224) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant Al-16892) | en_US |
dc.publisher | Elsevier BV | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/J.STR.2015.12.008 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Structural Basis of an N-Degron Adaptor with More Stringent Specificity | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Stein, Benjamin J. et al. “Structural Basis of an N-Degron Adaptor with More Stringent Specificity.” Structure 24, 2 (February 2016): 232–242 © 2016 Elsevier Ltd | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.mitauthor | Stein, Benjamin Joseph | |
dc.contributor.mitauthor | Grant, Robert A. | |
dc.contributor.mitauthor | Sauer, Robert T. | |
dc.contributor.mitauthor | Baker, Tania | |
dc.relation.journal | Structure | 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 |
dc.date.updated | 2018-06-06T13:32:40Z | |
dspace.orderedauthors | Stein, Benjamin J.; Grant, Robert A.; Sauer, Robert T.; Baker, Tania A. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-2246-2674 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1719-5399 | |
dspace.mitauthor.error | true | |
mit.license | PUBLISHER_CC | en_US |