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, Marie A. Hollenhorst, D. Judy Shon, Katherine H. Tiemeyer, Victor Attah, Catherine Kwon, Carolyn R. Bertozzi, Michael J. Ferracane, Mark A. Lemmon, Rommie E. Amaro and Stacy A. Malaker ()
Additional contact information
Joann Chongsaritsinsuk: Yale University
Alexandra D. Steigmeyer: Yale University
Keira E. Mahoney: Yale University
Mia A. Rosenfeld: University of California, San Diego
Taryn M. Lucas: Yale University
Courtney M. Smith: Yale University School of Medicine
Alice Li: Yale University School of Medicine
Deniz Ince: Yale University
Fiona L. Kearns: University of California, San Diego
Alexandria S. Battison: Yale University
Marie A. Hollenhorst: Stanford University
D. Judy Shon: Stanford University
Katherine H. Tiemeyer: Stanford University
Victor Attah: Yale University
Catherine Kwon: Yale University
Carolyn R. Bertozzi: Stanford University
Michael J. Ferracane: University of Redlands
Mark A. Lemmon: Yale University School of Medicine
Rommie E. Amaro: University of California, San Diego
Stacy A. Malaker: Yale University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41756-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41756-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41756-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().