Comparative multiplexed interactomics of SARS-CoV-2 and homologous coronavirus non-structural proteins identifies unique and shared host-cell dependencies

BioRxiv : the Preprint Server for Biology
Jonathan P DaviesLars Plate

Abstract

Human coronaviruses (hCoV) have become a threat to global health and society, as evident from the SARS outbreak in 2002 caused by SARS-CoV-1 and the most recent COVID-19 pandemic caused by SARS-CoV-2. Despite high sequence similarity between SARS-CoV-1 and -2, each strain has distinctive virulence. A better understanding of the basic molecular mechanisms mediating changes in virulence is needed. Here, we profile the virus-host protein-protein interactions of two hCoV non-structural proteins (nsps) that are critical for virus replication. We use tandem mass tag-multiplexed quantitative proteomics to sensitively compare and contrast the interactomes of nsp2 and nsp4 from three betacoronavirus strains: SARS-CoV-1, SARS-CoV-2, and hCoV-OC43 - an endemic strain associated with the common cold. This approach enables the identification of both unique and shared host cell protein binding partners and the ability to further compare the enrichment of common interactions across homologs from related strains. We identify common nsp2 interactors involved in endoplasmic reticulum (ER) Ca 2+ signaling and mitochondria biogenesis. We also identifiy nsp4 interactors unique to each strain, such as E3 ubiquitin ligase complexes for SARS-CoV-1 and...Continue Reading

Citations

Feb 13, 2021·Pathogens·Alejandro Flores-AlanisRosario Morales-Espinosa
May 28, 2021·Frontiers in Molecular Biosciences·Nadide AltincekicAndreas Schlundt

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Datasets Mentioned

BETA
AY278741

Methods Mentioned

BETA
interaction studies
affinity purification
glycosylation
affinity
transfections
ubiquitination
co-immunoprecipitation
Co-IPs
nucleotide exchange
Protein Assay

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