PXD009758

PXD009758 is an original dataset announced via ProteomeXchange.

Title	MS analysis of an FGE-PDI complex
Description	Multiple Sulfatase Deficiency (MSD) is a fatal, inherited lysosomal storage disorder characterised by reduced activities of all cellular sulfatases in patients. Sulfatases require a unique post-translational modification of an active site cysteine to formylglycine that is catalysed by the Formylglycine Generating Enzyme (FGE). FGE mutations leading to MSD affect the intracellular protein stability that determines residual enzyme activity and defines disease severity in MSD patients. Here, we show that Protein Disulfide Isomerase (PDI) plays a pivotal role in the recognition and quality control of MSD-causing FGE variants. Overexpression of PDI reduces the residual activity of unstable FGE variants, whereas inhibition of PDI function rescues the residual activity of sulfatases in MSD fibroblasts. Analysing a covalent complex consisting of PDI and a FGE variant by LC-MALDI mass spectrometry allowed to determine the molecular signature for FGE recognition by PDI. Our findings highlight the role of PDI as a disease modifier in MSD, which may be relevant also for other ER-associated protein folding pathologies.
HostingRepository	PRIDE
AnnounceDate	2018-07-04
AnnouncementXML	Submission_2018-07-30_01:27:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bernhard Schmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	ultraflex

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-11 05:44:55	ID requested
1	2018-07-03 23:42:49	announced
⏵ 2	2018-07-30 01:27:49	announced	Updated publication reference for PubMed record(s): 29972788.

Schlotawa L, Wachs M, Bernhard O, Mayer FJ, Dierks T, Schmidt B, Radhakrishnan K, Recognition and ER Quality Control of Misfolded Formylglycine-Generating Enzyme by Protein Disulfide Isomerase. Cell Rep, 24(1):27-37.e4(2018) [pubmed]

curator keyword: Biological

submitter keyword: PDI, FGE, Multiple Sulfatase Deficiency

Bernhard Schmidt
contact affiliation	Protein Analytics Lab, Department of Cellular Biochemistry, University Medical Center Göttingen, Germany
contact email	bschmid@gwdg.de
lab head
Bernhard Schmidt
contact affiliation	University Medical Center Göttingen
contact email	bschmid@gwdg.de
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/2018/07/PXD009758

PRIDE project URI

• PRIDE
  1. PXD009758
     1. Label: PRIDE project
     2. Name: MS analysis of an FGE-PDI complex