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Record W4391596910 · doi:10.1021/acscentsci.3c01598

Molecular Insights into O-Linked Sialoglycans Recognition by the Siglec-Like SLBR-N (SLBR<sub>UB10712</sub>) of <i>Streptococcus gordonii</i>

2024· article· en· W4391596910 on OpenAlexaff
Cristina Di Carluccio, Linda Cerofolini, Miguel A. M. Moreira, Frédéric Rosu, Luis Padilla‐Cortés, Giulia Roxana Gheorghita, Zhuojia Xu, Abhishek Santra, Hai Yu, Shinji Yokoyama, Taylor E. Gray, Chris D. St. Laurent, Yoshiyuki Manabe, Xi Chen, Koichi Fukase, Matthew S. Macauley, Antonio Molinaro, Tiehai Li, Barbara A. Bensing, Roberta Marchetti, Valérie Gabelica, Marco Fragai, Alba Silipo

Bibliographic record

VenueACS Central Science · 2024
Typearticle
Languageen
FieldMedicine
TopicStreptococcal Infections and Treatments
Canadian institutionsUniversity of Alberta
FundersHORIZON EUROPE Marie Sklodowska-Curie ActionsH2020 European Research CouncilNational Natural Science Foundation of ChinaNational Institute of Dental and Craniofacial ResearchNational Institute of Allergy and Infectious DiseasesMinistero dell’Istruzione, dell’Università e della Ricerca
KeywordsStreptococcus gordoniiIsothermal titration calorimetryGlycanGlycobiologyChemistryBacterial adhesinGlycoproteinPlasma protein bindingBiochemistryComputational biologyBiologyEscherichia coliGene

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Streptococcus gordonii is a Gram-positive bacterial species that typically colonizes the human oral cavity, but can also cause local or systemic diseases. Serine-rich repeat (SRR) glycoproteins exposed on the S. gordonii bacterial surface bind to sialylated glycans on human salivary, plasma, and platelet glycoproteins, which may contribute to oral colonization as well as endocardial infections. Despite a conserved overall domain organization of SRR adhesins, the Siglec-like binding regions (SLBRs) are highly variable, affecting the recognition of a wide range of sialoglycans. SLBR-N from the SRR glycoprotein of S. gordonii UB10712 possesses the remarkable ability to recognize complex core 2 O -glycans. We here employed a multidisciplinary approach, including flow cytometry, native mass spectrometry, isothermal titration calorimetry, NMR spectroscopy from both protein and ligand perspectives, and computational methods, to investigate the ligand specificity and binding preferences of SLBR-N when interacting with mono- and disialylated core 2 O -glycans. We determined the means by which SLBR-N preferentially binds branched α2,3-disialylated core 2 O -glycans: a selected conformation of the 3′SLn branch is accommodated into the main binding site, driving the sTa branch to further interact with the protein. At the same time, SLBR-N assumes an open conformation of the CD loop of the glycan-binding pocket, allowing one to accommodate the entire complex core 2 O -glycan. These findings establish the basis for the generation of novel tools for the detection of specific complex O -glycan structures and pave the way for the design and development of potential therapeutics against streptococcal infections.

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 score0.054
Threshold uncertainty score0.633

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.001
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 head0.012
GPT teacher head0.263
Teacher spread0.251 · 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

Citations5
Published2024
Admission routes1
Has abstractyes

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