Evidence map›Paper›PMID 34505572›Full record

ArticleeLife2021

Structural basis for membrane recruitment of ATG16L1 by WIPI2 in autophagy.

Lisa M Strong, Chunmei Chang, Julia F Riley, C Alexander Boecker, Thomas G Flower, Cosmo Z Buffalo, Xuefeng Ren, Andrea Kh Stavoe, Erika Lf Holzbaur, James H Hurley

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026
    Review
  4. Article
  5. The Human Autophagy Core Complexes.Annual review of biochemistry · 2026
    Review
  6. Article
  7. ER membrane receptors engage core autophagy machinery to initiate ER-phagy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    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 3 institutions in 1 country.

Lisa M StrongDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.ORCID https://orcid.org/0000-0002-4293-8131
Chunmei ChangDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.ORCID https://orcid.org/0000-0002-5607-7985
Julia F RileyAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, United States.ORCID https://orcid.org/0000-0001-8518-9786
C Alexander BoeckerAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, United States.ORCID https://orcid.org/0000-0001-9701-5273
Thomas G FlowerDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.ORCID https://orcid.org/0000-0002-7890-6473
Cosmo Z BuffaloDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Xuefeng RenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Andrea Kh StavoeDepartment of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, United States.ORCID https://orcid.org/0000-0002-4073-4565
Erika Lf HolzbaurAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, United States.ORCID https://orcid.org/0000-0001-5389-4114
James H HurleyDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.ORCID https://orcid.org/0000-0001-5054-5445
QB3 · USResearch Network (United States) · USThe University of Texas Health Science Center at Houston · US

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Aina E. Cohen, KEITH O HODGSON · 2020 to 2026
$43.3M
The Autophagy Initiation ComplexesR01GM111730 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HURLEY, JAMES H · 2014 to 2021
$2.2M
Autophagy in aging and neurodegenerationR00NS109286 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI STAVOE, ANDREA · 2021 to 2023
$747k
NIGMS NIH HHS P30 GM133894NIGMS NIH HHS R01 GM111730NINDS NIH HHS R00 NS109286
6 · The paper itself

Abstract

Autophagy is a cellular process that degrades cytoplasmic cargo by engulfing it in a double-membrane vesicle, known as the autophagosome, and delivering it to the lysosome. The ATG12-5-16L1 complex is responsible for conjugating members of the ubiquitin-like ATG8 protein family to phosphatidylethanolamine in the growing autophagosomal membrane, known as the phagophore. ATG12-5-16L1 is recruited to the phagophore by a subset of the phosphatidylinositol 3-phosphate-binding seven-bladedß -propeller WIPI proteins. We determined the crystal structure of WIPI2d in complex with the WIPI2 interacting region (W2IR) of ATG16L1 comprising residues 207-230 at 1.85 Å resolution. The structure shows that the ATG16L1 W2IR adopts an alpha helical conformation and binds in an electropositive and hydrophobic groove between WIPI2 ß-propeller blades 2 and 3. Mutation of residues at the interface reduces or blocks the recruitment of ATG12-5-16 L1 and the conjugation of the ATG8 protein LC3B to synthetic membranes. Interface mutants show a decrease in starvation-induced autophagy. Comparisons across the four human WIPIs suggest that WIPI1 and 2 belong to a W2IR-binding subclass responsible for localizing ATG12-5-16 L1 and driving ATG8 lipidation, whilst WIPI3 and 4 belong to a second W34IR-binding subclass responsible for localizing ATG2, and so directing lipid supply to the nascent phagophore. The structure provides a framework for understanding the regulatory node connecting two central events in autophagy initiation, the action of the autophagic PI 3-kinase complex on the one hand and ATG8 lipidation on the other.

Indexed as

AutophagyAutophagosomesAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsCrystallographyHeLa CellsHumansHydrophobic and Hydrophilic InteractionsIntracellular MembranesMembrane ProteinsModels, MolecularPhosphate-Binding ProteinsPhosphatidylinositol 3-KinasePoint MutationProtein Conformation, alpha-HelicalProtein TransportATG16L1 protein, humanAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsGABARAPL2 protein, humanMembrane ProteinsPhosphate-Binding ProteinsPhosphatidylinositol 3-KinaseWIPI2 protein, humanautophagycell biologyhumanLC3mitophagyparkinson's diseasevesicle reconstitutionx-ray crystallography

Identifiers

PMID34505572
PMCPMC8455133
OpenAlexW3196608509

What OpenQuestion 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 OpenQuestion graph.