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Mechanism of Atg9 recruitment by Atg11 in the cytoplasm-to-vacuole targeting pathway

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dc.abstract.enAutophagy is a lysosomal degradation pathway for the removal of damaged and superfluous cytoplasmic material. This is achieved by the sequestration of this cargo material within double-membrane vesicles termed autophagosomes. Autophagosome formation is mediated by the conserved autophagy machinery. In selective autophagy, this machinery including the transmembrane protein Atg9 is recruited to specific cargo material via cargo receptors and the Atg11/FIP200 scaffold protein. The molecular details of the interaction between Atg11 and Atg9 are unclear, and it is still unknown how the recruitment of Atg9 is regulated. Here we employ NMR spectroscopy of the N-terminal disordered domain of Atg9 (Atg9-NTD) to map its interaction with Atg11 revealing that it involves two short peptides both containing a PLF motif. We show that the Atg9-NTD binds to Atg11 with an affinity of about 1 μM and that both PLF motifs contribute to the interaction. Mutation of the PLF motifs abolishes the interaction of the Atg9-NTD with Atg11, reduces the recruitment of Atg9 to the precursor aminopeptidase 1 (prApe1) cargo, and blocks prApe1 transport into the vacuole by the selective autophagy-like cytoplasm-to-vacuole (Cvt) targeting pathway while not affecting bulk autophagy. Our results provide mechanistic insights into the interaction of the Atg11 scaffold with the Atg9 transmembrane protein in selective autophagy and suggest a model where only clustered Atg11 when bound to the prApe1 cargo is able to efficiently recruit Atg9 vesicles.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorZawadzka-Kazimierczuk, Anna
dc.contributor.authorMartens, Sascha
dc.contributor.authorBanaś, Bartłomiej
dc.contributor.authorCoudevylle, Nicolas
dc.contributor.authorSchuschnig, Martina
dc.contributor.authorBaumann, Verena
dc.contributor.authorKoźmiński, Wiktor
dc.date.accessioned2024-01-25T11:26:13Z
dc.date.available2024-01-25T11:26:13Z
dc.date.copyright2022-01-08
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number2
dc.description.versionFINAL_PUBLISHED
dc.description.volume298
dc.identifier.doi10.1016/J.JBC.2022.101573
dc.identifier.issn0021-9258
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/112204
dc.identifier.weblinkhttps://api.elsevier.com/content/article/PII:S0021925822000138?httpAccept=text/xml
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.pages101573
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.ennuclear magnetic resonance
dc.subject.enintrinsically disordered proteins
dc.subject.enautophagy
dc.subject.enisothermal titration calorimetry
dc.subject.enyeast metabolism
dc.titleMechanism of Atg9 recruitment by Atg11 in the cytoplasm-to-vacuole targeting pathway
dc.typeJournalArticle
dspace.entity.typePublication