PXD036640 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Cross-linking mass spectrometry uncovers interactions between high-density lipoproteins and the SARS-CoV-2 spike glycoprotein |
Description | Multiple studies to date have shown that high-density lipoprotein (HDL) levels are reduced in patients with coronavirus disease 2019 (COVID-19), and that the extent of this reduction is associated with poor clinical outcomes. While lipoproteins are known to play a key role during the lifecycle of hepatitis C virus, the direct influence they have upon coronavirus (CoV) infections remains poorly understood. In this study we utilise cross-linking mass spectrometry (XL-MS) to determine circulating protein interactors of the severe acute respiratory syndrome (SARS)-CoV-2 spike glycoprotein. Spike was revealed to interact with HDL, through direct interactions with apolipoprotein (Apo)-A1, ApoC3 and ApoD, highlighting multiple modalities of how SARS-CoV-2 and HDL may interact. XL-MS of plasma isolated from COVID-19 patients uncovered HDL protein interaction networks, dominated by acute phase serum amyloid proteins (SAA), whereby serum amyloid A2 (SAA2) was shown to bind to ApoD. ApoD was confirmed to also interact with core apolipoproteins of both LDL and VLDL, suggesting that SARS-CoV-2 may bind multiple lipoprotein species. The interaction between ApoD and spike was further validated in cells using immunoprecipitation-MS, which uncovered a novel interaction between both ApoD and spike with membrane-associated progesterone receptor component 1 (PGRMC1). Mechanistically, XL-MS coupled with data-driven structural modelling determined that ApoD may interact within the receptor-binding domain (RBD) of spike, posing the hypothesis that ApoD may interfere with binding to the angiotensin-converting enzyme 2 (ACE2) receptor. However, utilising multiple cell-based assays we determined ApoD to have no effect upon viral replication or infectivity. |
HostingRepository | PRIDE |
AnnounceDate | 2023-07-20 |
AnnouncementXML | Submission_2023-07-20_12:09:22.461.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | SeanBurnap |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos; Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-12 05:31:36 | ID requested | |
⏵ 1 | 2023-07-20 12:09:23 | announced | |
2 | 2023-11-14 09:03:57 | announced | 2023-11-14: Updated project metadata. |
Publication List
Burnap SA, Ortega-Prieto AM, Jimenez-Guarde, ñ, o JM, Ali H, Takov K, Fish M, Shankar-Hari M, Giacca M, Malim MH, Mayr M, Cross-Linking Mass Spectrometry Uncovers Interactions Between High-Density Lipoproteins and the SARS-CoV-2 Spike Glycoprotein. Mol Cell Proteomics, 22(8):100600(2023) [pubmed] |
Keyword List
ProteomeXchange project tag: Sars-cov-2, Covid-19 |
submitter keyword: XLMS, COVID, Spike, SARS-CoV-2, HDL |
Contact List
ManuelMayr |
contact affiliation | King's College London |
contact email | manuel.mayr@kcl.ac.uk |
lab head | |
SeanBurnap |
contact affiliation | Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK |
contact email | sean.burnap@chem.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036640
- Label: PRIDE project
- Name: Cross-linking mass spectrometry uncovers interactions between high-density lipoproteins and the SARS-CoV-2 spike glycoprotein