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

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 prote

SUBMITTER: Chongsaritsinsuk J 

PROVIDER: S-EPMC10550946 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature