PXD039583-2

PXD039583 is an original dataset announced via ProteomeXchange.

Title	Glycosite mapping and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE
Description	Mucin-domain glycoproteins are densely O-glycosylated and play key 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 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 dynamic (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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:28:29.412.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexandra Steigmeyer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; O-glycosylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-20 03:33:18	ID requested
1	2023-09-27 12:35:03	announced
⏵ 2	2023-11-14 08:28:29	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: O-glycoprotein, TIM-1, cancer, mucinase, TIM-4, TIM-3, O-glycosylation, immune checkpoint, T-cell immunoglobulin and mucin-domain containing, LC-MS/MS, molecular dynamics, mucinome,mucin, O-glycoproteomics, mucin domain, checkpoint inhibitor, O-glycoprotease

Stacy A. Malaker
contact affiliation	Department of Chemistry, Yale University, New Haven, CT 06511, USA
contact email	stacy.malaker@yale.edu
lab head
Alexandra Steigmeyer
contact affiliation	Yale University, Department of Chemistry
contact email	alexandra.steigmeyer@yale.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/09/PXD039583

PRIDE project URI

• PRIDE
  1. PXD039583
     1. Label: PRIDE project
     2. Name: Glycosite mapping and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE