PXD005804

PXD005804 is an original dataset announced via ProteomeXchange.

Title	Comparative glycoproteomics of embryonic stem cells identifies new players in ricin toxicity
Description	Rapid advances in the fields of DNA-, RNA-, polypeptide-sequencing and metabolomics have markedly enhanced our understanding of fundamental biological processes. In contrast to other post-translational modifications (PTMs), the most abundant PTM, glycosylation, remains largely unexplored at the proteome scale because of a scarcity of technologies for profiling the immensely complex glycoproteome. We developed a novel quantitative approach for the identification of intact glycopeptides from comparative proteomic data-sets, allowing us to not only identify complex sugar structures but also to directly map them to the corresponding glycosylation sites in the associated proteins at the proteome scale. Applying this method to human and murine embryonic stem cells, we were able to nearly double the number of all experimentally confirmed glycoproteins, including the identification of completely unknown glycosylation sites, multiple glycosylated stemness factors and the elucidation of evolutionary conserved core as well as species-specific glycoproteins in embryonic stem cells. Specificity of our method was confirmed in sister stem cells carrying repairable mutations in enzymes required for fucosylation, Fut9 and Slc35c1. Since ablation of fucosylation confers cellular resistance towards the bioweapon ricin (see accompanying paper), our method also allowed us to directly identify the proteins that carry the terminal fucosylation code for ricin toxicity; genetic mutations in these proteins functionally confirmed their role in ricin killing. This novel comparative and high-throughput glycoproteomics platform should allow for entirely novel insights in protein glycosylation and sugar modifications involved in nearly all biological systems.
HostingRepository	PRIDE
AnnounceDate	2017-09-25
AnnouncementXML	Submission_2017-10-02_06:09:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gerhard Duernberger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; N-acetylhexosaminylated; N-acetylaminogalactosylated; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-30 04:41:23	ID requested
1	2017-09-25 08:12:17	announced
⏵ 2	2017-10-02 06:09:42	announced	Updated publication reference for PubMed record(s): 28959962.

Stadlmann J, Taubenschmid J, Wenzel D, Gattinger A, D, ü, rnberger G, Dusberger F, Elling U, Mach L, Mechtler K, Penninger JM, Comparative glycoproteomics of stem cells identifies new players in ricin toxicity. Nature, 549(7673):538-542(2017) [pubmed]

curator keyword: Biological

submitter keyword: Stem cells, glycosylation, glycoproteomics

Josef Penninger
contact affiliation	IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.
contact email	Josef.Penninger@imba.oeaw.ac.at
lab head
Gerhard Duernberger
contact affiliation	GMI/IMP/IMBA
contact email	gerhard.duernberger@imp.ac.at
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/2017/09/PXD005804

PRIDE project URI

• PRIDE
  1. PXD005804
     1. Label: PRIDE project
     2. Name: Comparative glycoproteomics of embryonic stem cells identifies new players in ricin toxicity