Evidence map›Paper›PMID 36778266›Full record

ArticlebioRxiv : the preprint server for biology2023

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, Deniz Ince, Fiona L Kearns, Alexandria S Battison, Marie A Hollenhorst, D Judy Shon and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Joann ChongsaritsinsukDepartment of Chemistry, Yale University, New Haven, CT 06511, USA.
Alexandra D SteigmeyerDepartment of Chemistry, Yale University, New Haven, CT 06511, USA.
Keira E MahoneyDepartment of Chemistry, Yale University, New Haven, CT 06511, USA.
Mia A RosenfeldDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Taryn M LucasDepartment of Chemistry, Yale University, New Haven, CT 06511, 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.
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.
Katherine H TiemeyerDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
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.
Michael J FerracaneDepartment of Chemistry, University of Redlands, Redlands, CA 92373, USA.
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Stacy A MalakerDepartment of Chemistry, Yale University, New Haven, CT 06511, USA.

Funding

Project 5: Pandemic Virus Helicase InhibitorsU19AI171954 · NIAID · UNIVERSITY OF MINNESOTA · PI Donghoon Chung · 2022 to 2026
$100.9M
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 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 checkpoint inhibitors in cancer. However, their dense O-glycosylation remains enigmatic both in terms of glycoproteomic landscape and structural dynamics, primarily due to the challenges associated with studying mucin domains. Here, we present a mucinase (SmE) and demonstrate its ability to selectively cleave along the mucin glycoprotein backbone, similar to others of its kind. Unlike other mucinases, though, SmE harbors the unique ability to cleave at residues bearing extremely complex glycans which enabled improved mass spectrometric analysis of several mucins, including the entire TIM family. With this information in-hand, we performed molecular dynamics (MD) simulations of TIM-3 and -4 to demonstrate how glycosylation affects structural features of these proteins. Overall, we present a powerful workflow to better understand the detailed molecular structures of the mucinome.

Identifiers

PMID36778266
PMCPMC9915616

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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.