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 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 anal

SUBMITTER: Chongsaritsinsuk J 

PROVIDER: S-EPMC9915616 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature