PXD022215 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-28 01:46:23 | ID requested | |
⏵ 1 | 2021-07-30 04:21:05 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
ProteomeXchange project tag: Covid-19 |
submitter keyword: Golgi,SARS-CoV-2, COPI, S protein |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022215
- Label: PRIDE project
- Name: Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation