Evidence map›Paper›PMID 33393463›Full record

ArticleeLife2021

Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral form for nutrient uptake.

Marc A Schureck, Joseph E Darling, Alan Merk, Jinfeng Shao, Geervani Daggupati, Prakash Srinivasan, Paul Dominic B Olinares, Michael P Rout, Brian T Chait, Kurt Wollenberg and 2 more

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 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
8.4field-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

36 citing papers in PubMed, 50 citations in OpenAlex.

  1. Atomic clarity: how structural biology is shaping blood-stage malaria vaccines.Transactions of the Royal Society of Tropical Medicine and Hygiene · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Microorganisms · 2024
    Article
  13. Article
  14. Review
  15. bioRxiv : the preprint server for biology · 2024
    Article
  16. Article
  17. Iron transport pathways in the human malaria parasiteFrontiers in cellular and infection microbiology · 2024
    Article
  18. Review
  19. Unique Properties of Nutrient Channels onPathogens (Basel, Switzerland) · 2023
    Review
  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

12 authors at 4 institutions in 2 countries.

Marc A SchureckLaboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.
Joseph E DarlingLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Alan MerkLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Jinfeng ShaoLaboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.
Geervani DaggupatiDepartment of Molecular Microbiology and Immunology, and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.
Prakash SrinivasanDepartment of Molecular Microbiology and Immunology, and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.
Paul Dominic B OlinaresLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, United States.ORCID 0000-0002-3429-6618
Michael P RoutLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States.
Brian T ChaitLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, United States.
Kurt WollenbergOffice of Cyber Infrastructure & Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
Sriram SubramaniamDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.ORCID 0000-0003-4231-4115
Sanjay A DesaiLaboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.ORCID 0000-0003-2150-2483
National Institutes of Health · USRockefeller University · USJohns Hopkins University · USUniversity of British Columbia · CA

Funding

The Plasmodial Surface Anion Channel And Malaria Parasite Nutrient AcquisitionZIAAI000882 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DESAI, SANJAY A · 2009 to 2025
$20.5M
TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular NeighborhoodsP41GM109824 · NIGMS · ROCKEFELLER UNIVERSITY · PI ROUT, MICHAEL P · 2014 to 2023
$18.8M
National Resource for Mass Spectrom of Biological MacromoleculesP41GM103314 · NIGMS · ROCKEFELLER UNIVERSITY · PI CHAIT, BRIAN T · 2012 to 2017
$9.9M
NIGMS NIH HHS P41 GM103314NIGMS NIH HHS P41 GM109824NIH HHS P41 GM103314
6 · The paper itself

Abstract

Malaria parasites use the RhopH complex for erythrocyte invasion and channel-mediated nutrient uptake. As the member proteins are unique to Plasmodium spp., how they interact and traffic through subcellular sites to serve these essential functions is unknown. We show that RhopH is synthesized as a soluble complex of CLAG3, RhopH2, and RhopH3 with 1:1:1 stoichiometry. After transfer to a new host cell, the complex crosses a vacuolar membrane surrounding the intracellular parasite and becomes integral to the erythrocyte membrane through a PTEX translocon-dependent process. We present a 2.9 Å single-particle cryo-electron microscopy structure of the trafficking complex, revealing that CLAG3 interacts with the other subunits over large surface areas. This soluble complex is tightly assembled with extensive disulfide bonding and predicted transmembrane helices shielded. We propose a large protein complex stabilized for trafficking but poised for host membrane insertion through large-scale rearrangements, paralleling smaller two-state pore-forming proteins in other organisms.

Indexed as

ErythrocytesGenes, ProtozoanMultigene FamilyNutrientsPlasmodium falciparumNutrientscryo-EMerythrocyte invasioninfectious diseasemalariamicrobiologymolecular biophysicsnutrient uptakeP. falciparumpore-forming proteinsprotein structurestructural biology

Identifiers

PMID33393463
PMCPMC7840181
OpenAlexW3118289127

What OpenQuestion holds

Textmetadata
LicenceCC0
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.