PXD049174

PXD049174 is an original dataset announced via ProteomeXchange.

Title	A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis
Description	Dolichol is a lipid critical for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. It is commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires a three-step detour involving additional metabolites, where SRD5A3 catalyzes only the second reaction. The first and third steps are performed by DHRSX, whose gene resides on the pseudoautosomal regions of the X and Y chromosomes. Accordingly, we report a pseudoautosomal-recessive disease presenting as a congenital disorder of glycosylation in patients with missense variants in DHRSX (DHRSX-CDG). Of note, DHRSX has a unique dual substrate and cofactor specificity, allowing it to act as a NAD+-dependent dehydrogenase and as a NADPH-dependent reductase in two non-consecutive steps. Thus, our work reveals unexpected complexity in the terminal steps of dolichol biosynthesis. Furthermore, we provide insights into the mechanism by which dolichol metabolism defects contribute to disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:44:33.455.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD049174
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Francesco Caligiore
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Hex1HexNAc2 N4-glycosylated asparagine; Hex7HexNAc2 N4-glycosylated asparagine; Hex3HexNAc2 N4-glycosylated asparagine; Hex2HexNAc2 N4-glycosylated asparagine; Hex9HexNAc2 N4-glycosylated asparagine; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-05 03:44:37	ID requested
1	2024-06-12 00:28:59	announced
⏵ 2	2024-10-22 06:44:34	announced	2024-10-22: Updated project metadata.

Wilson MP, Kentache T, Althoff CR, Schulz C, de Bettignies G, Mateu Cabrera G, Cimbalistiene L, Burnyte B, Yoon G, Costain G, Vuillaumier-Barrot S, Cheillan D, Rymen D, Rychtarova L, Hansikova H, Bury M, Dewulf JP, Caligiore F, Jaeken J, Cantagrel V, Van Schaftingen E, Matthijs G, Foulquier F, Bommer GT, A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. Cell, 187(14):3585-3601.e22(2024) [pubmed]

10.6019/PXD049174;

10.1016/j.cell.2024.04.041;

submitter keyword: Lipid droplets, Congenital Disorders of Glycosylation, Polyprenal, N-glycosylation, Dolichal, Pseudoautosomal Region,Dolichol, Polyprenol

Guido T.
contact affiliation	de Duve Institute UCLouvain and WELBIO
contact email	guido.bommer@uclouvain.be
lab head
Francesco Caligiore
contact affiliation	UCLouvain
contact email	francesco.caligiore@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/2024/06/PXD049174

PRIDE project URI

• PRIDE
  1. PXD049174
     1. Label: PRIDE project
     2. Name: A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis