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Record W4400264930 · doi:10.1038/s41467-024-48921-x

Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2

2024· article· en· W4400264930 on OpenAlexfundno aff
Huanyu Li, A.C.W. Pike, Irina Lotsaris, Gamma Chi, Jesper S. Hansen, Sarah C. Lee, Karin E. J. Rödström, Simon R. Bushell, David Speedman, Adam Evans, Dong Wang, Didi He, Leela Shrestha, Chady Nasrallah, Nicola A. Burgess-Brown, Robert J. Vandenberg, Timothy R. Dafforn, Elisabeth P. Carpenter, David B. Sauer

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAmino Acid Enzymes and Metabolism
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilInnovative Medicines InitiativeKungliga Tekniska HögskolanEuropean CommissionResearch Councils UKMedical Research CouncilEuropean Federation of Pharmaceutical Industries and AssociationsMcGill UniversityDiamond Light SourceWellcome Trust
KeywordsProlineTransporterAmino acidChemistryBiochemistryProtein structureReceptorCytoplasmCoronavirus disease 2019 (COVID-19)Peptide sequenceCell biologyBiologyGeneMedicine

Abstract

fetched live from OpenAlex

Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes that link substrate release and opening of the cytoplasmic gate and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.

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 score0.004
Threshold uncertainty score0.007

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.014
GPT teacher head0.278
Teacher spread0.264 · 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

Citations13
Published2024
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicAmino Acid Enzymes and MetabolismFrench-language works237,207