PXD036640

PXD036640 is an original dataset announced via ProteomeXchange.

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:49.450.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sean Burnap
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

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.

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]

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: XLMS, COVID, Spike, SARS-CoV-2, HDL

Manuel Mayr
contact affiliation	King's College London
contact email	manuel.mayr@kcl.ac.uk
lab head
Sean Burnap
contact affiliation	Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK
contact email	sean.burnap@chem.ox.ac.uk
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/2023/07/PXD036640

PRIDE project URI

• PRIDE
  1. PXD036640
     1. Label: PRIDE project
     2. Name: Cross-linking mass spectrometry uncovers interactions between high-density lipoproteins and the SARS-CoV-2 spike glycoprotein