PXD038629

PXD038629 is an original dataset announced via ProteomeXchange.

Title	Selennoprotein S interacts with the replication and transcription complex of the SARS-CoV-2 by binding nsp7
Description	The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replicates and evades detection by using endoplasmic reticulum (ER) membranes and their associated protein machineries. Among these hijacked human ER proteins is selenoprotein S, which usually takes part in the ER protein degradation pathway, NFkB signaling, and regulation of cytokines secretion. While the role of selenoprotein S in the viral life cycle is not yet known, it has been reported that it interacts with SARS-CoV-2 non-structural protein 7 (nsp7), a viral protein essential for the reproduction of SARS-CoV-2. However, it was unknown if selenoprotein S and nsp7 interact directly and whether the two proteins can still interact when nsp7 is bound to the virus' replication machinery. Using biochemical assays, we show that selenoprotein S indeed binds directly to nsp7. In addition, we find that selenoprotein S can also bind nsp7 when it is in a complex with the coronavirus's minimal replication complex: nsp7, nsp8 and the RNA-dependent RNA polymerase. Using cross-linking experiments, we mapped the interactions of selenoprotein S and nsp7 in the replication complex and show that the hydrophobic segment of selenoprotein S is essential for binding nsp7. This arrangement leaves an extended helix and the intrinsically disordered segment of selenoprotein S exposed and free to potentially recruit additional proteins to the replication complex. Thus, selenoprotein S is shown to directly interact with the viral replication complex, which places this human protein at the heart of viral replication.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:17:20.252.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Farid Ghelichkhani
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-07 06:42:47	ID requested
1	2023-03-10 18:11:19	announced
⏵ 2	2023-11-14 08:17:21	announced	2023-11-14: Updated project metadata.

Ghelichkhani F, Gonzalez FA, Kapitonova MA, Rozovsky S, Selenoprotein S Interacts with the Replication and Transcription Complex of SARS-CoV-2 by Binding nsp7. J Mol Biol, 435(8):168008(2023) [pubmed]

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

submitter keyword: selenos, nsp12, nsp8, COVID-19, VIMP

Sharon Rozovsky
contact affiliation	Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, 19716 USA
contact email	rozovsky@udel.edu
lab head
Farid Ghelichkhani
contact affiliation	University of Delaware
contact email	farid@udel.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038629
     1. Label: PRIDE project
     2. Name: Selennoprotein S interacts with the replication and transcription complex of the SARS-CoV-2 by binding nsp7