Evidence map›Paper›PMID 37794035›Full record

ArticleNature communications2023

Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE.

Joann Chongsaritsinsuk, Alexandra D Steigmeyer, Keira E Mahoney, Mia A Rosenfeld, Taryn M Lucas, Courtney M Smith, Alice Li, Deniz Ince, Fiona L Kearns, Alexandria S Battison and 10 more

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed.

  1. Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Deep Learning Prediction of O-Glycopeptide Tandem Mass Spectra Enhances O-Glycoproteomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  11. Mucinase fromFrontiers in microbiology · 2026
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Joann Chongsaritsinsuk *Department of Chemistry, Yale University, New Haven, CT, 06511, USA.
Alexandra D Steigmeyer *Department of Chemistry, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0001-9805-4012
Keira E Mahoney *Department of Chemistry, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0003-4561-9838
Mia A Rosenfeld *Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-8961-8231
Taryn M LucasDepartment of Chemistry, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0002-1697-0939
Courtney M SmithYale Cancer Biology Institute and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, 06520, USA.
Alice LiYale Cancer Biology Institute and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, 06520, USA.
Deniz InceDepartment of Chemistry, Yale University, New Haven, CT, 06511, USA.
Fiona L KearnsDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
Alexandria S BattisonDepartment of Chemistry, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0002-4381-873X
Marie A HollenhorstDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.
D Judy ShonDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0001-8379-6195
Katherine H TiemeyerDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0001-5691-8281
Victor AttahDepartment of Chemistry, Yale University, New Haven, CT, 06511, USA.
Catherine KwonDepartment of Chemistry, Yale University, New Haven, CT, 06511, USA.
Carolyn R BertozziDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0003-4482-2754
Michael J FerracaneDepartment of Chemistry, University of Redlands, Redlands, CA, 92373, USA.ORCID http://orcid.org/0000-0002-3007-3126
Mark A LemmonYale Cancer Biology Institute and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, 06520, USA.ORCID http://orcid.org/0000-0002-3379-5319
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-9275-9553
Stacy A MalakerDepartment of Chemistry, Yale University, New Haven, CT, 06511, USA. stacy.malaker@yale.edu.ORCID http://orcid.org/0000-0003-2382-5067

Funding

Project 5: Pandemic Virus Helicase InhibitorsU19AI171954 · NIAID · UNIVERSITY OF MINNESOTA · PI Donghoon Chung · 2022 to 2026
$100.9M
Understanding Signaling by Non-Canonical Receptor Tyrosine KinasesR35GM122485 · NIGMS · YALE UNIVERSITY · PI Mark A Lemmon · 2017 to 2026
$7.9M
Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
Training in Multi-Scale Analysis of Biological Structure and FunctionT32EB009380 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrew D. McCulloch, Padmini Rangamani · 2009 to 2026
$4.8M
Investigating the Surface GlycoproteomeR01CA200423 · NCI · STANFORD UNIVERSITY · PI Carolyn Bertozzi · 2015 to 2026
$3.8M
Predoctoral Training at the Interface Chemistry and BiologyT32GM149444 · NIGMS · YALE UNIVERSITY · PI Jason Michael Crawford · 2023 to 2026
$2.2M
Toward understanding the role of altered glycosylation in cancerR35GM147039 · NIGMS · YALE UNIVERSITY · PI Stacy Alyse Malaker · 2022 to 2026
$2.0M
A MULTISCALE APPROACH TO TARGET THE ACHILLES HEEL OF P53 CANCER MUTANTS (Equipment Supplement)R01GM132826 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2019 to 2022
$1.3M
Biochemistry of Platelet DesialylationK99HL156029 · NHLBI · STANFORD UNIVERSITY · PI HOLLENHORST, MARIE · 2021 to 2024
$670k
NCI NIH HHS R01 CA200423NHLBI NIH HHS K99 HL156029NIAID NIH HHS U19 AI171954NIBIB NIH HHS T32 EB009380NIGMS NIH HHS R01 GM132826NIGMS NIH HHS R35 GM122485NIGMS NIH HHS R35 GM147039NIGMS NIH HHS T32 GM067543NIGMS NIH HHS T32 GM149444
6 · The paper itself

Abstract

Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of biological functions. In particular, the T cell immunoglobulin and mucin-domain containing family of proteins (TIM-1, -3, -4) decorate immune cells and act as key regulators in cellular immunity. However, their dense O-glycosylation remains enigmatic, primarily due to the challenges associated with studying mucin domains. Here, we demonstrate that the mucinase SmE has a unique ability to cleave at residues bearing very complex glycans. SmE enables improved mass spectrometric analysis of several mucins, including the entire TIM family. With this information in-hand, we perform molecular dynamics (MD) simulations of TIM-3 and -4 to understand how glycosylation affects structural features of these proteins. Finally, we use these models to investigate the functional relevance of glycosylation for TIM-3 function and ligand binding. Overall, we present a powerful workflow to better understand the detailed molecular structures and functions of the mucinome.

Indexed as

Hepatitis A Virus Cellular Receptor 2MucinsPolysaccharide-LyasesPolysaccharidesHepatitis A Virus Cellular Receptor 2hyaluronate lyaseMucinsPolysaccharide-LyasesPolysaccharides

Identifiers

PMID37794035
PMCPMC10550946

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.