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dc.contributor.authorPras, Anita
dc.contributor.authorHouben, Bert
dc.contributor.authorAprile, Francesco A
dc.contributor.authorSeinstra, Renée
dc.contributor.authorGallardo, Rodrigo
dc.contributor.authorJanssen, Leen
dc.contributor.authorHogewerf, Wytse
dc.contributor.authorGallrein, Christian
dc.contributor.authorDe Vleeschouwer, Matthias
dc.contributor.authorMata‐Cabana, Alejandro
dc.contributor.authorKoopman, Mandy
dc.contributor.authorStroo, Esther
dc.contributor.authorde Vries, Minke
dc.contributor.authorLouise Edwards, Samantha
dc.contributor.authorKirstein, Janine
dc.contributor.authorVendruscolo, Michele
dc.contributor.authorFalsone, Salvatore Fabio
dc.contributor.authorRousseau, Frederic
dc.contributor.authorSchymkowitz, Joost
dc.contributor.authorNollen, Ellen A A
dc.date.accessioned2021-10-07T08:24:51Z
dc.date.available2021-10-07T08:24:51Z
dc.date.issued2021-10-07
dc.date.submitted2020-12-23
dc.identifier.issn0261-4189
dc.identifier.issn1460-2075
dc.identifier.otherembj2020107568
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329074
dc.descriptionFunder: Ubbo Emmius fonds
dc.descriptionFunder: Boehringer Ingelheim Fonds (BIF); Id: http://dx.doi.org/10.13039/501100001645
dc.descriptionFunder: Cornelis de Cock
dc.descriptionFunder: FP7 People Marie‐Curie Actions (PEOPLE)
dc.descriptionFunder: BCN Brain RUG
dc.descriptionFunder: KU Leuven, Post‐doctoral Mandate PDM/20/150 and the Industrial Research Fund; Id: http://dx.doi.org/10.13039/501100004040
dc.description.abstractAbstract: While aggregation‐prone proteins are known to accelerate aging and cause age‐related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG‐4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid‐promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG‐4 to neutralize charge. Our data indicate that MOAG‐4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation‐prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age‐related protein toxicity.
dc.languageen
dc.subjectEMBO27
dc.subjectEMBO32
dc.subjectArticle
dc.subjectArticles
dc.subjectamyloid
dc.subjectMOAG‐4
dc.subjectprotein aggregation
dc.subjectprotein quality control
dc.subjectSERF
dc.titleThe cellular modifier MOAG‐4/SERF drives amyloid formation through charge complementation
dc.typeArticle
dc.date.updated2021-10-07T08:24:51Z
prism.publicationNameThe EMBO Journal
dc.identifier.doi10.17863/CAM.76519
dcterms.dateAccepted2021-09-01
rioxxterms.versionofrecord10.15252/embj.2020107568
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.contributor.orcidPras, Anita [0000-0003-2752-152X]
dc.contributor.orcidHouben, Bert [0000-0002-6750-011X]
dc.contributor.orcidAprile, Francesco A [0000-0002-5040-4420]
dc.contributor.orcidSeinstra, Renée [0000-0001-5083-399X]
dc.contributor.orcidJanssen, Leen [0000-0002-1973-304X]
dc.contributor.orcidGallrein, Christian [0000-0002-7623-2778]
dc.contributor.orcidMata‐Cabana, Alejandro [0000-0002-0179-2746]
dc.contributor.orcidKoopman, Mandy [0000-0003-1429-2078]
dc.contributor.orcidLouise Edwards, Samantha [0000-0002-7722-5959]
dc.contributor.orcidKirstein, Janine [0000-0003-4990-2497]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.contributor.orcidFalsone, Salvatore Fabio [0000-0002-3724-5824]
dc.contributor.orcidRousseau, Frederic [0000-0002-9189-7399]
dc.contributor.orcidSchymkowitz, Joost [0000-0003-2020-0168]
dc.contributor.orcidNollen, Ellen A A [0000-0003-3740-6373]
pubs.funder-project-idFP7 Ideas European Research Council (FP7 Ideas) (281622)
pubs.funder-project-idNWO|Aard‐ en Levenswetenschappen, Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW‐NWO) (83609001, 015014005)
pubs.funder-project-idDeutsche Forschungsgemeinschaft (DFG) (KI‐1988/5‐1)
pubs.funder-project-idEuropean Union's Horizon 2020 Framework Programme ERC Grant agreement (647458)
pubs.funder-project-idFlanders Institute for Biotechnology (VIB) (C0401)
pubs.funder-project-idthe Agency for Innovation by Science and Technology, IWT (60839, 141546)
pubs.funder-project-idFonds Wetenschappelijk Onderzoek (FWO) (AKUL/15/34‐G0H1716N, G0C0320N)
pubs.funder-project-idIWT PHD fellowship (141546)
pubs.funder-project-idUK Research and Innovation (Future Leaders Fellowship) (MR/S033947/1)
pubs.funder-project-idAlzheimer’s Society, UK (511)


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