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Record W3159257193 · doi:10.1371/journal.pbio.3001237

Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies

2021· article· en· W3159257193 on OpenAlexafffund
Xing Zhu, Dhiraj Mannar, Shanti Swaroop Srivastava, Alison Berezuk, Jean‐Philippe Demers, James W. Saville, Karoline Leopold, Wei Li, Dimiter S. Dimitrov, Katharine S. Tuttle, Steven Zhou, Sagar Chittori, Sriram Subramaniam

Bibliographic record

VenuePLoS Biology · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of British Columbia
FundersGenome British ColumbiaCanada Excellence Research Chairs, Government of CanadaTRIUMFHuman Frontier Science Program
KeywordsBiologyNeutralizationMutantCryo-electron microscopyInfectivityMutationEpitopeNeutralizing antibodyProtein structureAntibodySpike (software development)Spike ProteinBiophysicsPlasma protein bindingSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)VirologyReceptorCell biologyCoronavirus disease 2019 (COVID-19)VirusBiochemistryGeneticsGene

Abstract

fetched live from OpenAlex

The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.

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 score0.100
Threshold uncertainty score0.391

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 head0.056
GPT teacher head0.365
Teacher spread0.308 · 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

Citations200
Published2021
Admission routes2
Has abstractyes

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