{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(9)"],"submitter":["Zhu K"],"funding":["National Natural Science Foundation of China"],"pubmed_abstract":["Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2<sup>ZYG11B</sup> 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<sup>ZYG11B</sup> remains unknown. Here, we determined the crystal structure of CUL2<sup>ZYG11B</sup> 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<su"],"journal":["Acta pharmaceutica Sinica. B"],"pagination":["4164-4173"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11413682"],"repository":["biostudies-literature"],"pubmed_title":["SARS-CoV-2 ORF10 hijacking ubiquitination machinery reveals potential unique drug targeting sites."],"pmcid":["PMC11413682"],"pubmed_authors":["Song L","Yuan S","Luo Z","Zhu K","Wang T","Mi W","Gao X","Cui S","Hua L","Qin B","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"SARS-CoV-2 ORF10 hijacking ubiquitination machinery reveals potential unique drug targeting sites.","description":"Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2<sup>ZYG11B</sup> 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<sup>ZYG11B</sup> remains unknown. Here, we determined the crystal structure of CUL2<sup>ZYG11B</sup> 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<su","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-01T19:28:58.464Z","creation":"2025-04-04T02:19:21.195Z"},"accession":"S-EPMC11413682","cross_references":{"pubmed":["39309499"],"doi":["10.1016/j.apsb.2024.05.018"]}}