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Chongsaritsinsuk, Joann; Steigmeyer, Alexandra D.; Mahoney, Keira E.; Rosenfeld, Mia A.; Lucas, Taryn M.; Smith, Courtney M.; Li, Alice; Ince, Deniz; Kearns, Fiona L.; Battison, Alexandria S.; Hollenhorst, Marie A.; Judy Shon, D.; Tiemeyer, Katherine H.; Attah, Victor; Kwon, Catherine; Bertozzi, Carolyn R.; Ferracane, Michael J.; Lemmon, Mark A.; Amaro, Rommie E.; Malaker, Stacy A.

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

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  • Media type: E-Article
  • Title: Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE
  • Contributor: Chongsaritsinsuk, Joann; Steigmeyer, Alexandra D.; Mahoney, Keira E.; Rosenfeld, Mia A.; Lucas, Taryn M.; Smith, Courtney M.; Li, Alice; Ince, Deniz; Kearns, Fiona L.; Battison, Alexandria S.; Hollenhorst, Marie A.; Judy Shon, D.; Tiemeyer, Katherine H.; Attah, Victor; Kwon, Catherine; Bertozzi, Carolyn R.; Ferracane, Michael J.; Lemmon, Mark A.; Amaro, Rommie E.; Malaker, Stacy A.
  • Published: Springer Science and Business Media LLC, 2023
  • Published in: Nature Communications, 14 (2023) 1
  • Language: English
  • DOI: 10.1038/s41467-023-41756-y
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Access State: Open Access