Evidence map›Paper›PMID 26712012›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair.

Michelle L Parker, Diana M Penarete-Vargas, Phineas T Hamilton, Amandine Guérin, Jitender P Dubey, Steve J Perlman, Furio Spano, Maryse Lebrun, Martin J Boulanger

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Invasion ofProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  6. Article
  7. New Avenues to DesignFrontiers in immunology · 2022
    Article
  8. Article
  9. Article
  10. Frontiers in immunology · 2020
    Article
  11. Article
  12. Strategies Developed byFrontiers in microbiology · 2019
    Review
  13. Article
  14. RON4Scientific reports · 2017
    Article
  15. Review
  16. Article
  17. Genomics of apicomplexan parasites.Critical reviews in biochemistry and molecular biology · 2017
    Review
  18. 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 5 institutions in 4 countries.

Michelle L ParkerDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8P 5C2, Canada;
Diana M Penarete-VargasUMR 5235, CNRS Université Montpellier, 34095 Montpellier, France;
Phineas T HamiltonDepartment of Biology, University of Victoria, Victoria, BC, V8P 5C2, Canada;
Amandine GuérinUMR 5235, CNRS Université Montpellier, 34095 Montpellier, France;
Jitender P DubeyAnimal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705-2350;
Steve J PerlmanDepartment of Biology, University of Victoria, Victoria, BC, V8P 5C2, Canada;
Furio SpanoDepartment of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome 00161, Italy.
Maryse LebrunUMR 5235, CNRS Université Montpellier, 34095 Montpellier, France; mboulang@uvic.ca mylebrun@univ-montp2.fr.
Martin J BoulangerDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8P 5C2, Canada; mboulang@uvic.ca mylebrun@univ-montp2.fr.
University of Victoria · CACentre National de la Recherche Scientifique · FRIstituto Superiore di Sanità · ITUnited States Department of Agriculture · USUniversité de Montpellier · FR

Funding

Canadian Institutes of Health Research MOP82915
6 · The paper itself

Abstract

Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2L1. High-resolution crystal structures of TgAMA4 in the apo and TgRON2L1-bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA-RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite-host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA-RON2 pairs and apicomplexan invasive stages.

Indexed as

Host-Parasite InteractionsAnimalsMiceModels, MolecularParasitesPhylogenyProtein BindingProtozoan ProteinsToxoplasmaProtozoan Proteinsrhoptry neck protein 2, Toxoplasma gondiiApicomplexainvasionmoving junctionToxoplasma gondiiX-ray crystallography

Identifiers

PMID26712012
PMCPMC4720339
OpenAlexW2208235309

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.