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dc.contributor.authorMcCormack, EA
dc.contributor.authorAltschuler, GM
dc.contributor.authorDekker, C
dc.contributor.authorFilmore, H
dc.contributor.authorWillison, KR
dc.date.accessioned2018-08-29T11:09:46Z
dc.date.issued2009-08-07
dc.identifier1
dc.identifier.citationJOURNAL OF MOLECULAR BIOLOGY, 2009, 391 pp. 192 - 206
dc.identifier.issn0022-2836
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2398
dc.identifier.eissn1089-8638
dc.identifier.doi10.1016/j.jmb.2009.06.003
dc.description.abstractThe eukaryotic chaperonin-containing TCP-1 (CCT) folds the cytoskeletal protein actin. The folding mechanism of this 16-subunit, 1-MDa machine is poorly characterised due to the absence of quantitative in vitro assays. We identified phosducin-like protein 2, Plp2p (=PLP2), as an ATP-elutable binding partner of yeast CCT while establishing the CCT interactome. In a novel in vitro CCT-ACT1 folding assay that is functional under physiological conditions, PLP2 is a stimulatory co-factor. In a single ATP-driven cycle, PLP2-CCT-ACT1 complexes yield 30-fold more native actin than CCT-ACT1 complexes. PLP2 interacts directly with ACT1 through the C-terminus of its thioredoxin fold and the CCT-binding subdomain 4 of actin. The in vitro CCT-ACT1-PLP2 folding cycle of the preassembled complex takes 90 s at 30 degrees C, several times slower than the canonical chaperonin GroEL. The specific interactions between PLP2, CCT and ACTI in the yeast-component in vitro system and the pronounced stimulatory effect of PLP2 on actin folding are consistent with in vivo genetic approaches demonstrating an essential and positive role for PLP2 in cellular processes involving actin in Saccharomyces cerevisiae. In mammalian systems, however, several members of the PLP family, including human PDCL3, the orthologue of PLP2, have been shown to be inhibitory toward CCT-mediated folding of actin in vivo and in vitro. Here, using a rabbit-reticulocyte-derived in vitro translation system, we found that inhibition of p-actin folding by PDCL3 can be relieved by exchanging its acidic C-terminal extension for that of PLP2. It seems that additional levels of regulatory control of CCT activity by this PLP have emerged in higher eukaryotes. (c) 2009 Elsevier Ltd. All rights reserved.
dc.format.extent192 - 206
dc.languageeng
dc.language.isoeng
dc.publisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
dc.titleYeast Phosducin-Like Protein 2 Acts as a Stimulatory Co-Factor for the Folding of Actin by the Chaperonin CCT via a Ternary Complex
dc.typeJournal Article
rioxxterms.versionofrecord10.1016/j.jmb.2009.06.003
rioxxterms.licenseref.startdate2009-08-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJOURNAL OF MOLECULAR BIOLOGY
pubs.notesaffiliation: Willison, KR (Reprint Author), Inst Canc Res, Chester Beatty Labs, Sect Cell & Mol Biol, Prot Folding & Assembly Team, 237 Fulham Rd, London SW3 6JB, England. McCormack, Elizabeth A.; Altschuler, Gabriel M.; Dekker, Carien; Filmore, Heather; Willison, Keith R., Inst Canc Res, Chester Beatty Labs, Sect Cell & Mol Biol, Prot Folding & Assembly Team, London SW3 6JB, England. keywords: molecular chaperones; chaperonin-containing TCP-1; actin; phosducin-like proteins; ATP kinetics keywords-plus: EUKARYOTIC CYTOSOLIC CHAPERONIN; BETA-ACTIN; CYTOPLASMIC CHAPERONIN; SUBSTRATE-BINDING; CONTAINING TCP-1; TUBULIN; MECHANISM; SUBUNITS; CONFORMATIONS; INTERACTS research-areas: Biochemistry & Molecular Biology web-of-science-categories: Biochemistry & Molecular Biology author-email: [email protected] orcid-numbers: Rada, Heather/0000-0003-1477-419X funding-acknowledgement: Institute of Cancer Research, Human Frontiers Science Program [RGP63/2004]; Cancer Research UK and Engineering and Physical Sciences Research Council; Institute of Cancer Research PhD studentship funding-text: This work was funded by the Institute of Cancer Research, Human Frontiers Science Program (RGP63/2004), Cancer Research UK and Engineering and Physical Sciences Research Council through a platform grant. G.M.A. was funded by an Institute of Cancer Research PhD studentship. We thank Angela Paul for mass spectrometric analysis and Maurizio Valeri for mAbs. number-of-cited-references: 47 times-cited: 15 usage-count-last-180-days: 0 usage-count-since-2013: 7 journal-iso: J. Mol. Biol. doc-delivery-number: 479HX unique-id: ISI:000268651400014 da: 2018-08-29
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Chromatin Regulation
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Chromatin Regulation
pubs.volume391
pubs.embargo.termsNot known
icr.researchteamChromatin Regulationen_US
dc.contributor.icrauthorWillison, Keithen


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