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Record W3107491342 · doi:10.7554/elife.59018

Structural ordering of the Plasmodium berghei circumsporozoite protein repeats by inhibitory antibody 3D11

2020· article· en· W3107491342 on OpenAlexafffund
Iga Kucharska, Elaine Thai, Ananya Srivastava, John L. Rubinstein, Régis Pomès, Jean‐Philippe Julien

Bibliographic record

VenueeLife · 2020
Typearticle
Languageen
FieldMedicine
TopicMalaria Research and Control
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersBiological and Environmental ResearchNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesNational Cancer InstituteNatural Sciences and Engineering Research Council of CanadaCanada Research ChairsNational Institutes of HealthOntario Ministry of Economic Development, Job Creation and TradeHospital for Sick ChildrenSick Kids FoundationOffice of ScienceCanada Foundation for InnovationOntario Research FoundationCanadian Institutes of Health ResearchCompute CanadaCanadian Institute for Advanced ResearchBrookhaven National LaboratoryArgonne National LaboratoryU.S. Department of Energy
KeywordsCircumsporozoite proteinPlasmodium bergheiPlasmodium falciparumMonoclonal antibodyBiologyAntibodyVirologyPlasmodium (life cycle)Malaria vaccineEpitopeStructural motifComputational biologyMalariaGeneticsImmunologyBiochemistryParasite hosting

Abstract

fetched live from OpenAlex

Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 – the leading malaria vaccine against P. falciparum (Pf) – has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to P. berghei CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.139
Threshold uncertainty score0.324

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.263
Teacher spread0.249 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations30
Published2020
Admission routes2
Has abstractyes

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