PXD034131

PXD034131 is an original dataset announced via ProteomeXchange.

Title	Oncogenic CALR Mutant C-terminus Mediates Dual Binding to the Thrombopoietin Receptor Triggering Complex Dimerization and Activation
Description	Calreticulin (CALR) is a master lectin chaperone that guides the proper folding of integral membrane proteins in the endoplasmic reticulum. In healthy cells, CALR transiently and non-specifically interacts with thousands of immature N-glycosylated proteins through its N-terminal glycan-binding domain. Conversely, frameshift mutants of CALR turn into rogue cytokine by acquiring the ability to stably and specifically interact with the Thrombopoietin Receptor (TpoR). Strikingly, this interaction induces activation of TpoR leading to myeloproliferative neoplasms, blood cancers resulting from the overproduction of blood cells. Using a multidisciplinary approach, we unveil how the CALR frameshift mutations result in structural overhaul of the entire protein and identify the structural basis of its acquired specificty for TpoR. We further describe the mechanisms by zhich complex formation triggers TpoR dimerization and activation. In addition, we provide the first complete dynamic conformational footprints of both wild-type and mutant CALR and identify novel potentially targetable sites.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:50.977.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicolas Papadopoulos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-26 01:16:39	ID requested
1	2023-04-11 08:08:40	announced
⏵ 2	2023-11-14 08:56:51	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: HDx-MS

Stefan N. Constantinescu
contact affiliation	Universite Catholique de Louvain and de Duve Institute, Brussels, Belgium Ludwig Institute for Cancer Research, Brussels, Belgium
contact email	stefan.constantinescu@bru.licr.org
lab head
Nicolas Papadopoulos
contact affiliation	de Duve Institute Ludwig Cancer Research UCLouvain
contact email	nicolas.papadopoulos@uclouvain.be
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/2023/04/PXD034131

PRIDE project URI

• PRIDE
  1. PXD034131
     1. Label: PRIDE project
     2. Name: Oncogenic CALR Mutant C-terminus Mediates Dual Binding to the Thrombopoietin Receptor Triggering Complex Dimerization and Activation