Evidence map›Paper›PMID 36396942›Full record

ArticleNature microbiology2022

PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum.

Stephen W Scally, Tony Triglia, Cindy Evelyn, Benjamin A Seager, Michał Pasternak, Pailene S Lim, Julie Healer, Niall D Geoghegan, Amy Adair, Wai-Hong Tham and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
14.6field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 81 citations in OpenAlex.

  1. Semi-synthesis of the C-terminal region ofRSC chemical biology · 2026
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  17. bioRxiv : the preprint server for biology · 2025
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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

13 authors at 2 institutions in 1 country.

Stephen W ScallyThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Tony TrigliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Cindy EvelynThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-8818-0258
Benjamin A SeagerThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Michał PasternakThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0001-5407-4273
Pailene S LimThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Julie HealerThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Niall D GeogheganThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0001-9884-0769
Amy AdairThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-2952-7987
Wai-Hong ThamThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0001-7950-8699
Laura F DagleyThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0003-4171-3712
Kelly L RogersThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID http://orcid.org/0000-0002-6755-0221
Alan F CowmanThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. cowman@wehi.edu.au.ORCID http://orcid.org/0000-0001-5145-9004
The University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

Wellcome Trust 206515/Z/17/Z
6 · The paper itself

Abstract

The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes, and an essential step in this process involves the ligand PfRh5, which forms a complex with cysteine-rich protective antigen (CyRPA) and PfRh5-interacting protein (PfRipr) (RCR complex) and binds basigin on the host cell. We identified a heteromeric disulfide-linked complex consisting of P. falciparum Plasmodium thrombospondin-related apical merozoite protein (PfPTRAMP) and P. falciparum cysteine-rich small secreted protein (PfCSS) and have shown that it binds RCR to form a pentameric complex, PCRCR. Using P. falciparum lines with conditional knockouts, invasion inhibitory nanobodies to both PfPTRAMP and PfCSS, and lattice light-sheet microscopy, we show that they are essential for merozoite invasion. The PCRCR complex functions to anchor the contact between merozoite and erythrocyte membranes brought together by strong parasite deformations. We solved the structure of nanobody-PfCSS complexes to identify an inhibitory epitope. Our results define the function of the PCRCR complex and identify invasion neutralizing epitopes providing a roadmap for structure-guided development of these proteins for a blood stage malaria vaccine.

Indexed as

Blood Group AntigensMalaria, FalciparumMalaria VaccinesCysteineEpitopesErythrocytesHumansPlasmodium falciparumBlood Group AntigensCysteineEpitopesMalaria Vaccines

Identifiers

PMID36396942
PMCPMC9712106
OpenAlexW4309219084

What OpenQuestion holds

Textmetadata
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.