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dc.contributor.authorKardon, Julia R
dc.contributor.authorMoroco, Jamie A
dc.contributor.authorEngen, John R
dc.contributor.authorBaker, Tania A
dc.date.accessioned2021-10-27T20:34:28Z
dc.date.available2021-10-27T20:34:28Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/1721.1/136243
dc.description.abstract© 2020, eLife Sciences Publications Ltd. All rights reserved. Mitochondria control the activity, quality, and lifetime of their proteins with an autonomous system of chaperones, but the signals that direct substrate-chaperone interactions and outcomes are poorly understood. We previously discovered that the mitochondrial AAA+ protein unfoldase ClpX (mtClpX) activates the initiating enzyme for heme biosynthesis, 5-aminolevulinic acid synthase (ALAS), by promoting cofactor incorporation. Here, we ask how mtClpX accomplishes this activation. Using S. cerevisiae proteins, we identified sequence and structural features within ALAS that position mtClpX and provide it with a grip for acting on ALAS. Observation of ALAS undergoing remodeling by mtClpX revealed that unfolding is limited to a region extending from the mtClpX-binding site to the active site. Unfolding along this path is required for mtClpX to gate cofactor binding to ALAS. This targeted unfolding contrasts with the global unfolding canonically executed by ClpX homologs and provides insight into how substrate-chaperone interactions direct the outcome of remodeling.
dc.language.isoen
dc.publishereLife Sciences Publications, Ltd
dc.relation.isversionof10.7554/ELIFE.54387
dc.rightsCreative Commons Attribution 4.0 International license
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceeLife
dc.titleMitochondrial ClpX activates an essential biosynthetic enzyme through partial unfolding
dc.typeArticle
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biology
dc.contributor.departmentHoward Hughes Medical Institute
dc.relation.journaleLife
dc.eprint.versionFinal published version
dc.type.urihttp://purl.org/eprint/type/JournalArticle
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.date.updated2021-07-14T12:30:24Z
dspace.orderedauthorsKardon, JR; Moroco, JA; Engen, JR; Baker, TA
dspace.date.submission2021-07-14T12:30:26Z
mit.journal.volume9
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Needed


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