SARS-CoV-2 ORF10 hijacking ubiquitination machinery reveals potential unique drug targeting sites.

ABSTRACT: Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2^ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase, is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity, leading to degradation of IFT46, a protein component of the intraflagellar transport (IFT) complex B. This results in dysfunctional cilia, which explains certain symptoms that are specific to COVID-19. However, the precise molecular mechanism of how ORF10 recognizes CUL2^ZYG11B remains unknown. Here, we determined the crystal structure of CUL2^ZYG11B complexed with the N-terminal extension (NTE) of SARS-CoV-2 ORF10 (2.9 Å). The structure reveals that the ORF10 N-terminal heptapeptide (NTH) mimics the Gly/N-degron to bind CUL2

SUBMITTER: Zhu K 

PROVIDER: S-EPMC11413682 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature