Evidence map›Paper›PMID 30982432›Full record

ArticleAutophagy2020

Human LC3 and GABARAP subfamily members achieve functional specificity via specific structural modulations.

Nidhi Jatana, David B Ascher, Douglas E V Pires, Rajesh S Gokhale, Lipi Thukral

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Guideline
  2. Review
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  5. Autophagy · 2026
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  14. Autophagy3D: a comprehensive autophagy structure database.Database : the journal of biological databases and curation · 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

5 authors at 2 institutions in 5 countries.

Nidhi JatanaCSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
David B AscherDepartment of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Melbourne, Victoria, Australia.ORCID 0000-0003-2948-2413
Douglas E V PiresDepartment of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Melbourne, Victoria, Australia.ORCID 0000-0002-3004-2119
Rajesh S GokhaleCSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Lipi ThukralCSIR-Institute of Genomics and Integrative Biology, New Delhi, India.ORCID 0000-0002-1961-039X
Institute of Genomics and Integrative Biology · INThe University of Melbourne · AU

Funding

Medical Research Council MR/M026302/1
6 · The paper itself

Abstract

Autophagy is a conserved adaptive cellular pathway essential to maintain a variety of physiological functions. Core components of this machinery are the six human Atg8 orthologs that initiate formation of appropriate protein complexes. While these proteins are routinely used as indicators of autophagic flux, it is presently not possible to discern their individual biological functions due to our inability to predict specific binding partners. In our attempts towards determining downstream effector functions, we developed a computational pipeline to define structural determinants of human Atg8 family members that dictate functional diversity. We found a clear evolutionary separation between human LC3 and GABARAP subfamilies and also defined a novel sequence motif responsible for their specificity. By analyzing known protein structures, we observed that functional modules or microclusters reveal a pattern of intramolecular network, including distinct hydrogen bonding of key residues (F52/Y49; a subset of HP2) that may directly modulate their interaction preferences. Multiple molecular dynamics simulations were performed to characterize how these proteins interact with a common protein binding partner, PLEKHM1. Our analysis showed remarkable differences in binding modes via intrinsic protein dynamics, with PLEKHM1-bound GABARAP complexes showing less fluctuations and higher number of contacts. We further mapped 373 genomic variations and demonstrated that distinct cancer-related mutations are likely to lead to significant structural changes. Our findings present a quantitative framework to establish factors underlying exquisite specificity of human Atg8 proteins, and thus facilitate the design of precise modulators.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid MotifsAmino Acid SequenceApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBinding SitesEvolution, MolecularHumansHydrogen BondingMicrotubule-Associated ProteinsModels, MolecularMutationNeoplasmsProtein BindingStructure-Activity RelationshipAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsGABARAPL2 protein, humanGABARAP protein, humanMAP1LC3A protein, humanMicrotubule-Associated ProteinsPLEKHM1 protein, humanAutophagyevolutionfunctional diversityGABARAPLC3molecular dynamicsnon-covalent interactionsorthologs

Identifiers

PMID30982432
PMCPMC6984608
OpenAlexW2938646552

What OpenQuestion holds

Textmetadata
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.