Evidence map›Paper›PMID 22982544›Full record

ArticleJournal of structural biology2012

Structural characterization and inhibition of the Plasmodium Atg8-Atg3 interaction.

Adelaide U P Hain, Ryan R Weltzer, Holly Hammond, Bamini Jayabalasingham, Rhoel R Dinglasan, David R M Graham, David R Colquhoun, Isabelle Coppens, Jürgen Bosch

Abstract read
In one paragraph

Article in Journal of structural biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
3.3field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.

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  13. Microbiology spectrum · 2022
    Article
  14. Review
  15. Review
  16. Atg3 promotes Atg8 lipidation via altering lipid diffusion and rearrangement.Protein science : a publication of the Protein Society · 2020
    Article
  17. Review
  18. Structural Analysis ofFrontiers in bioengineering and biotechnology · 2019
    Article
  19. Article
  20. Article
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

9 authors at 2 institutions in 1 country.

Adelaide U P HainDepartment of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.
Ryan R Weltzer
Holly Hammond
Bamini Jayabalasingham
Rhoel R Dinglasan
David R M Graham
David R Colquhoun
Isabelle Coppens
Jürgen Bosch
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

ZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI BELCHER, HAROLYN MILLICENT EDITH · 1985 to 2007
$37.3M
Small molecule protein-glycan inhib. as malaria transmission-blocking therapueticR01AI082587 · NIAID · JOHNS HOPKINS UNIVERSITY · PI DINGLASAN, RHOEL DAVID RAMOS · 2009 to 2013
$1.9M
Metamorphosis and development of Plasmodium within liver cellsR56AI080631 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COPPENS, ISABELLE · 2010 to 2010
$410k
Glycobiological Analysis of Plasmodium-Vector Host InteractionsK22AI077707 · NIAID · JOHNS HOPKINS UNIVERSITY · PI DINGLASAN, RHOEL DAVID RAMOS · 2009 to 2010
$270k
NCRR NIH HHS M01 RR000052NCRR NIH HHS RR00052NIAID NIH HHS K22 AI077707NIAID NIH HHS K22AI077707-02NIAID NIH HHS R01 AI082587NIAID NIH HHS R01AI082587-01NIAID NIH HHS R56 AI080631
6 · The paper itself

Abstract

The autophagy-related proteins are thought to serve multiple functions in Plasmodium and are considered essential to parasite survival and development. We have studied two key interacting proteins, Atg8 and Atg3, of the autophagy pathway in Plasmodium falciparum. These proteins are vital for the formation and elongation of the autophagosome and essential to the process of macroautophagy. Autophagy may be required for conversion of the sporozoite into erythrocytic-infective merozoites and may be crucial for other functions during asexual blood stages. Here we describe the identification of an Atg8 family interacting motif (AIM) in Plasmodium Atg3, which binds Plasmodium Atg8. We determined the co-crystal structure of PfAtg8 with a short Atg3¹⁰³⁻¹¹⁰ peptide, corresponding to this motif, to 2.2 Å resolution. Our in vitro interaction studies are in agreement with our X-ray crystal structure. Furthermore they suggest an important role for a unique Apicomplexan loop absent from human Atg8 homologues. Prevention of the protein-protein interaction of full length PfAtg8 with PfAtg3 was achieved at low micromolar concentrations with a small molecule, 1,2,3-trihydroxybenzene. Together our structural and interaction studies represent a starting point for future antimalarial drug discovery and design for this novel protein-protein interaction.

Indexed as

Amino Acid SequenceAntimalarialsAutophagyBinding SitesCrystallography, X-RayDrug DiscoveryEscherichia coliMolecular Docking SimulationMolecular Sequence DataOligopeptidesPlasmodium falciparumProtein BindingProtein Structure, TertiaryProtozoan ProteinsPyrogallolRecombinant ProteinsAntimalarialsOligopeptidesProtozoan ProteinsPyrogallolRecombinant ProteinsUbiquitin-Conjugating Enzymes

Identifiers

PMID22982544
PMCPMC3496014
OpenAlexW2013899838

What OpenQuestion holds

Textmetadata
LicenceTDM
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.