Evidence map›Paper›PMID 25742002›Full record

ArticlePloS one2015

Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2.

Christopher A MacRaild, Milan Zachrdla, Dean Andrew, Bankala Krishnarjuna, Jiří Nováček, Lukáš Žídek, Vladimír Sklenář, Jack S Richards, James G Beeson, Robin F Anders and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.0field-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

25 citing papers in PubMed, 43 citations in OpenAlex.

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  5. Naturally acquired IgG responses toFrontiers in immunology · 2024
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  10. Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.Proceedings of the National Academy of Sciences of the United States of America · 2020
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  11. Optimization of aProceedings of the National Academy of Sciences of the United States of America · 2020
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  16. Article
  17. Article
  18. Disordered epitopes as peptide vaccines.Peptide science (Hoboken, N.J.) · 2018
    Review
  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

11 authors at 5 institutions in 2 countries.

Christopher A MacRaildMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
Milan ZachrdlaNCBR, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic; CEITEC, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic.
Dean AndrewCentre for Biomedical Research, Burnet Institute, Melbourne, Victoria, 3004, Australia.
Bankala KrishnarjunaMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
Jiří NováčekNCBR, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic; CEITEC, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic.
Lukáš ŽídekNCBR, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic; CEITEC, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic.
Vladimír SklenářNCBR, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic; CEITEC, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic.
Jack S RichardsCentre for Biomedical Research, Burnet Institute, Melbourne, Victoria, 3004, Australia.
James G BeesonCentre for Biomedical Research, Burnet Institute, Melbourne, Victoria, 3004, Australia.
Robin F AndersDepartment of Biochemistry, La Trobe University, Victoria, 3086, Australia.
Raymond S NortonMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Australia.
Burnet Institute · AUMonash University · AUCentral European Institute of Technology – Masaryk University · CZMasaryk University · CZLa Trobe University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.

Indexed as

Antigens, ProtozoanNuclear Magnetic Resonance, BiomolecularPlasmodium falciparumProtein ConformationProtozoan ProteinsAntigens, Protozoanmerozoite surface protein 2, PlasmodiumProtozoan Proteins

Identifiers

PMID25742002
PMCPMC4351039
OpenAlexW1964818141

What OpenQuestion holds

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LicenceCC BY
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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.