PXD022215-1

PXD022215 is an original dataset announced via ProteomeXchange.

Title	Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
Description	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds the cell surface protein ACE2 to mediate fusion of the viral membrane with target cells1-4. S comprises a large external domain, a transmembrane domain (TMD) and a short cytoplasmic tail5,6. To elucidate the intracellular trafficking of S protein in host cells we applied proteomics to identify cellular factors that interact with its cytoplasmic tail. We confirm interactions with components of the COPI, COPII and SNX27/retromer vesicle coats, and with FERM domain actin regulators and the WIPI3 autophagy component. The interaction with COPII promotes efficient exit from the endoplasmic reticulum (ER), and although COPI-binding should retain S in the early Golgi system where viral budding occurs, the binding is weakened by a suboptimal histidine residue in the recognition motif. As a result, S leaks to the surface where it accumulates as it lacks an endocytosis motif of the type found in many other coronaviruses7-10. It is known that when at the surface S can direct cell:cell fusion leading to the formation of multinucleate syncytia7-9. Thus, the trafficking signals in the cytoplasmic tail of S protein indicate that syncytia formation is not an inadvertent by-product of infection but rather a key aspect of the replicative cycle of SARS-CoV-2 and potential cause of pathological symptoms.
HostingRepository	PRIDE
AnnounceDate	2021-07-30
AnnouncementXML	Submission_2021-07-30_04:21:05.010.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-28 01:46:23	ID requested
⏵ 1	2021-07-30 04:21:05	announced

Dataset with its publication pending

ProteomeXchange project tag: Covid-19

submitter keyword: Golgi,SARS-CoV-2, COPI, S protein

Sean Munro
contact affiliation	MRC Laboratory of Molecular Biology, Cell Biology, Cambridge
contact email	sean@mrc-lmb.cam.ac.uk
lab head
Mark Skehel
contact affiliation	MRC LMB
contact email	mskehel@mrc-lmb.cam.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/2021/07/PXD022215

PRIDE project URI

• PRIDE
  1. PXD022215
     1. Label: PRIDE project
     2. Name: Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation