Evidence map›Paper›PMID 33845085›Full record

ArticleJournal of molecular biology2021

Phosphorylation of the LIR Domain of SCOC Modulates ATG8 Binding Affinity and Specificity.

Martina Wirth, Stephane Mouilleron, Wenxin Zhang, Eva Sjøttem, Yakubu Princely Abudu, Ashish Jain, Hallvard Lauritz Olsvik, Jack-Ansgar Bruun, Minoo Razi, Harold B J Jefferies and 5 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Martina WirthMolecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands(‡). Electronic address: m.b.wirth@lumc.nl.
Stephane MouilleronStructural Biology Science Technology Platforms, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Wenxin ZhangMolecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Eva SjøttemMolecular Cancer Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
Yakubu Princely AbuduMolecular Cancer Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
Ashish JainMolecular Cancer Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway; Department of Molecular Cell Biology, Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway(‡).
Hallvard Lauritz OlsvikMolecular Cancer Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
Jack-Ansgar BruunMolecular Cancer Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
Minoo RaziMolecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Harold B J JefferiesMolecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Rebecca LeeStructural Biology Science Technology Platforms, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Dhira JoshiPeptide Chemistry Science Technology Platforms, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Nicola O'ReillyPeptide Chemistry Science Technology Platforms, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Terje JohansenMolecular Cancer Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway. Electronic address: terje.johansen@uit.no.
Sharon A ToozeMolecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Molecular Cell Biology, Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway(‡). Electronic address: sharon.tooze@crick.ac.uk.
The Francis Crick Institute · GBUiT The Arctic University of Norway · NO

Funding

Cancer Research UK FC001187Cancer Research UK FC001999Medical Research Council FC001187Medical Research Council FC001999Wellcome Trust FC001187Wellcome Trust FC001999
6 · The paper itself

Abstract

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. 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. 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.

Indexed as

Amino Acid MotifsAmino Acid SequenceAnimalsApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyCarrier ProteinsHEK293 CellsHeLa CellsHumansMammalsMembrane ProteinsMicrotubule-Associated ProteinsPhosphorylationProtein BindingProtein DomainsProtein Serine-Threonine KinasesApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyCarrier ProteinsGABARAP protein, humanMembrane ProteinsMicrotubule-Associated ProteinsProtein Serine-Threonine KinasesSCOC protein, humanTBK1 protein, humanautophagybio-layer interferometrycrystal structureLIR motifphosphorylation

Identifiers

PMID33845085
PMCPMC8202330
OpenAlexW3154542321

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.