Evidence map›Paper›PMID 30936093›Full record

ArticleThe EMBO journal2019

Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy.

Leo J Dudley, Ainara G Cabodevilla, Agata N Makar, Martin Sztacho, Tim Michelberger, Joseph A Marsh, Douglas R Houston, Sascha Martens, Xuejun Jiang, Noor Gammoh

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

44 citing papers in PubMed, 74 citations in OpenAlex.

  1. Article
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  5. ZDHHC7-mediatedAutophagy · 2024
    Article
  6. Review
  7. Review
  8. ATG16L1 induces the formation of phagophore-like membrane cups.Nature structural & molecular biology · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Leo J DudleyCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ainara G CabodevillaCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Agata N MakarCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.ORCID 0000-0003-4661-1010
Martin SztachoDepartment of Biochemistry and Cell Biology, Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, Vienna, Austria.
Tim MichelbergerCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Joseph A MarshHuman Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Douglas R HoustonInstitute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Edinburgh, UK.
Sascha MartensDepartment of Biochemistry and Cell Biology, Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, Vienna, Austria.ORCID 0000-0003-3786-8199
Xuejun JiangCell Biology Department, Memorial Sloan Kettering Cancer Centre, New York, NY, USA.
Noor GammohCancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK noor.gammoh@igmm.ed.ac.uk.ORCID 0000-0001-9402-9581
Edinburgh Cancer Research · GBUniversity of Vienna · ATInstitute of Genetics and Cancer · GBMemorial Sloan Kettering Cancer Center · USUniversity of Edinburgh · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Mechanisms and Function of Autophagy in CancerR01CA166413 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI JIANG, XUEJUN · 2013 to 2023
$3.9M
Role of the ULK1 Complex in AutophagyR01GM113013 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI JIANG, XUEJUN · 2015 to 2018
$1.5M
Cancer Research UK 21586NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA166413NIGMS NIH HHS R01 GM113013
6 · The paper itself

Abstract

Membrane targeting of autophagy-related complexes is an important step that regulates their activities and prevents their aberrant engagement on non-autophagic membranes. ATG16L1 is a core autophagy protein implicated at distinct phases of autophagosome biogenesis. In this study, we dissected the recruitment of ATG16L1 to the pre-autophagosomal structure (PAS) and showed that it requires sequences within its coiled-coil domain (CCD) dispensable for homodimerisation. Structural and mutational analyses identified conserved residues within the CCD of ATG16L1 that mediate direct binding to phosphoinositides, including phosphatidylinositol 3-phosphate (PI3P). Mutating putative lipid binding residues abrogated the localisation of ATG16L1 to the PAS and inhibited LC3 lipidation. On the other hand, enhancing lipid binding of ATG16L1 by mutating negatively charged residues adjacent to the lipid binding motif also resulted in autophagy inhibition, suggesting that regulated recruitment of ATG16L1 to the PAS is required for its autophagic activity. Overall, our findings indicate that ATG16L1 harbours an intrinsic ability to bind lipids that plays an essential role during LC3 lipidation and autophagosome maturation.

Indexed as

AutophagyAnimalsAutophagy-Related ProteinsCell MembraneCells, CulturedEmbryo, MammalianEndosomesFibroblastsMiceMice, KnockoutPhosphate-Binding ProteinsPhosphatidylinositol Phosphatesrab GTP-Binding ProteinsUbiquitin-Conjugating EnzymesAtg16l1 protein, mouseAtg3 protein, mouseAutophagy-Related ProteinsPhosphate-Binding Proteinsphosphatidylinositol 3-phosphatePhosphatidylinositol PhosphatesRab33B protein, mouserab GTP-Binding ProteinsUbiquitin-Conjugating EnzymesWipi2 protein, mouseATG16L1autophagycoiled‐coil domainphagophorePI3P

Identifiers

PMID30936093
PMCPMC6484409
OpenAlexW2927870165

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.