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Record W2119228816 · doi:10.1073/pnas.1004148107

Architecture of Eph receptor clusters

2010· article· en· W2119228816 on OpenAlexafffund
Juha P. Himanen, L. Yermekbayeva, Peter W. Janes, John R. Walker, Kai Xu, Lakmali Atapattu, Kanagalaghatta R. Rajashankar, Anneloes Mensinga, Martin Lackmann, Dimitar B. Nikolov, Sirano Dhe‐Paganon

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2010
Typearticle
Languageen
FieldNeuroscience
TopicAxon Guidance and Neuronal Signaling
Canadian institutionsStructural Genomics ConsortiumUniversity of Toronto
FundersNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Health and Medical Research CouncilMedical Research CouncilOntario GenomicsNational Institutes of HealthKnut och Alice Wallenbergs StiftelseKarolinska InstitutetStiftelsen för Strategisk ForskningNational Center for Research ResourcesOntario Genomics InstituteGenome CanadaGlaxoSmithKlineOntario Innovation TrustWellcome TrustArgonne National LaboratoryU.S. Department of Energy
KeywordsErythropoietin-producing hepatocellular (Eph) receptorEphrinEPH receptor A2EctodomainCell biologyBiologyReceptor tyrosine kinaseSignal transductionReceptorBiochemistry

Abstract

fetched live from OpenAlex

Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. Here we present high-resolution structures of the complete EphA2 ectodomain and complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The structures reveal an elongated architecture with novel Eph/Eph interactions, both within and outside of the Eph ligand-binding domain, that suggest the molecular mechanism underlying Eph/ephrin clustering. Structure-function analysis, by using site-directed mutagenesis and cell-based signaling assays, confirms the importance of the identified oligomerization interfaces for Eph clustering.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.049
GPT teacher head0.307
Teacher spread0.258 · 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 source (direct Gemma or distilled Codex), 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

Citations269
Published2010
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicAxon Guidance and Neuronal SignalingFrench-language works237,207