PXD023072

PXD023072 is an original dataset announced via ProteomeXchange.

Title	Notch-Jagged signaling complex defined by an interaction mosaic
Description	The Notch signaling system links cellular fate to that of its neighbors, driving proliferation, apoptosis, and cell differentiation in metazoan organisms, whereas dysfunction leads to debilitating developmental disorders and cancers. Here we probe the molecular architecture of mammalian Notch1 full ectodomain in complex with the canonical ligand Jagged1 using cross-linking mass spectrometry (XL-MS). Our data reveals that three Jagged1 sites, C2-epidermal growth factor (EGF) 1, EGF10 and cysteine-rich domain (CRD), are in proximity to the Notch1 negative regulatory region (NRR) in the Notch1-Jagged1 full ectodomain complex. We verified direct interactions and identified additional interacting regions by quantitative-binding experiments. In addition, XL-MS and structural analysis reveal Notch1 and Jagged1 ectodomain intramolecular interactions and structural flexibility that support the formation of backfolded architectures. Together the data suggest a direct and intricate role for the different extracellular regions of Notch1 and Jagged1 in the activation and regulation of Notch1 signaling.
HostingRepository	PRIDE
AnnounceDate	2021-07-08
AnnouncementXML	Submission_2021-07-08_02:34:50.433.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Scheltema
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-11 06:42:19	ID requested
⏵ 1	2021-07-08 02:34:50	announced

Dataset with its publication pending

submitter keyword: Notch1, Jagged1, cell signaling, EGF repeats, protein-protein interaction, glycoprotein, cross-linking mass spectrometry, XlinkX/PD, PhoX

Richard Scheltema
contact affiliation	Utrecht University / Pharmaceutical Sciences Biomolecular Mass Spectrometry and Proteomics Padualaan 8 , 3584 CH Utrecht
contact email	r.a.scheltema@uu.nl
lab head
Richard Scheltema
contact affiliation	Utrecht University
contact email	r.a.scheltema@uu.nl
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/2021/07/PXD023072

PRIDE project URI

• PRIDE
  1. PXD023072
     1. Label: PRIDE project
     2. Name: Notch-Jagged signaling complex defined by an interaction mosaic