PXD050878

PXD050878 is an original dataset announced via ProteomeXchange.

Title	HCMV US2 co-opts TRC8 to degrade the ER-resident protein LMAN2L
Description	The human cytomegalovirus (HCMV) pUS2 glycoprotein exploits the host’s endoplasmic reticulum (ER)-associated degradation (ERAD) pathway to degrade MHC class I and prevent antigen presentation. Beyond MHC class I, pUS2 has been shown to target a range of cellular proteins for degradation, preventing their cell surface expression. Here we have identified a novel pUS2 target, ER-resident protein lectin mannose binding 2 like (LMAN2L). pUS2 expression was both necessary and sufficient for the downregulation of LMAN2L, which was dependent on the cellular E3 ligase TRC8. Given the hypothesised role of LMAN2L in the trafficking of glycoproteins, we employed proteomic plasma membrane profiling to measure LMAN2L-dependent changes at the cell surface. Known pUS2 target integrin alpha-6 (ITGA6) was downregulated from the surface of LMAN2L deficient cells. Overall, these results suggest a novelstrategy of pUS2-mediated protein degradation whereby pUS2 targets LMAN2L to impair trafficking of ITGA6. Given US2 can directly target other integrins, this single viral protein exhibits both direct and indirect mechanisms to downregulate integrins from the cell surface.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:46:51.905.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Weekes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-21 17:20:50	ID requested
1	2024-06-23 01:22:24	announced
⏵ 2	2024-10-22 06:46:59	announced	2024-10-22: Updated project metadata.

Hunter LM, Kite J, Fletcher-Etherington A, Nightingale K, Nobre L, Antrobus R, Fielding CA, Stanton RJ, Weekes MP, HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L. J Gen Virol, 105(4):(2024) [pubmed]

10.1099/jgv.0.001980;

submitter keyword: Cytomegalovirus, proteomics, protein trafficking, protein degradation, plasma membrane

Michael Weekes
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge
contact email	mpw1001@cam.ac.uk
lab head
Michael Weekes
contact affiliation	University of Cambridge
contact email	mpw1001@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050878
     1. Label: PRIDE project
     2. Name: HCMV US2 co-opts TRC8 to degrade the ER-resident protein LMAN2L