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PXD022215

PXD022215 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2021-07-30
AnnouncementXMLSubmission_2021-07-30_04:21:05.010.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMark Skehel
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-28 01:46:23ID requested
12021-07-30 04:21:05announced
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 affiliationMRC Laboratory of Molecular Biology, Cell Biology, Cambridge
contact emailsean@mrc-lmb.cam.ac.uk
lab head
Mark Skehel
contact affiliationMRC LMB
contact emailmskehel@mrc-lmb.cam.ac.uk
dataset submitter
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Dataset FTP location
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