Vis enkel innførsel

dc.contributor.authorWirth, Martina
dc.contributor.authorMouilleron, Stephane
dc.contributor.authorZhang, Wenxin
dc.contributor.authorAbudu, Yakubu Princely
dc.contributor.authorJain, Ashish
dc.contributor.authorOlsvik, Hallvard Lauritz
dc.contributor.authorBruun, Jack-Ansgar
dc.contributor.authorRazi, Minoo
dc.contributor.authorJefferies, Harold B.J.
dc.contributor.authorLee, Rebecca
dc.contributor.authorJoshi, Dhira
dc.contributor.authorO'Reilly, Nicola
dc.contributor.authorJohansen, Terje
dc.contributor.authorTooze, Sharon A
dc.date.accessioned2021-06-24T08:45:33Z
dc.date.available2021-06-24T08:45:33Z
dc.date.issued2021-04-24
dc.description.abstract<p>Autophagy is a highly conserved degradative pathway, essential for cellular homeostasis and implicated in diseases including cancer and neurodegeneration. Autophagy-related 8 (ATG8) proteins play a central role in autophagosome formation and selective delivery of cytoplasmic cargo to lysosomes by recruiting autophagy adaptors and receptors. The LC3-interacting region (LIR) docking site (LDS) of ATG8 proteins binds to LIR motifs present in autophagy adaptors and receptors. LIR-ATG8 interactions can be highly selective for specific mammalian ATG8 family members (LC3A-C, GABARAP, and GABARAPL1-2) and how this specificity is generated and regulated is incompletely understood. <p>We have identified a LIR motif in the Golgi protein SCOC (short coiled-coil protein) exhibiting strong binding to GABARAP, GABARAPL1, LC3A and LC3C. The residues within and surrounding the core LIR motif of the SCOC LIR domain were phosphorylated by autophagy-related kinases (ULK1-3, TBK1) increasing specifically LC3 family binding. More distant flanking residues also contributed to ATG8 binding. Loss of these residues was compensated by phosphorylation of serine residues immediately adjacent to the core LIR motif, indicating that the interactions of the flanking LIR regions with the LDS are important and highly dynamic. <p>Our comprehensive structural, biophysical and biochemical analyses support and provide novel mechanistic insights into how phosphorylation of LIR domain residues regulates the affinity and binding specificity of ATG8 proteins towards autophagy adaptors and receptors.en_US
dc.identifier.citationWirth M, Mouilleron S, Zhang W, Abudu YP, Jain Ashish Jain, Olsvik H, Bruun JA, Razi M, Jefferies HB, Lee R, Joshi D, O'Reilly N, Johansen T, Tooze SA. Phosphorylation of the LIR Domain of SCOC Modulates ATG8 Binding Affinity and Specificity. Journal of Molecular Biology (JMB). 2021;433(12):166987en_US
dc.identifier.cristinIDFRIDAID 1912440
dc.identifier.doi10.1016/j.jmb.2021.166987
dc.identifier.issn0022-2836
dc.identifier.issn1089-8638
dc.identifier.urihttps://hdl.handle.net/10037/21549
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Molecular Biology (JMB)
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/214448/Norway/Selective autophagy and cell signalling: Regulation of p62/SQSTM1 and functional studies of novel LIR-containing proteins//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/249884/Norway/Autophagy-regulated Signalosomes in Cellular Stress and Disease Pathways//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Molecular biology: 473en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Molekylærbiologi: 473en_US
dc.titlePhosphorylation of the LIR Domain of SCOC Modulates ATG8 Binding Affinity and Specificityen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel