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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
Structural insights into ORF10 recognition by ZYG11B
Bing Zhang1, Yao Li1, Qiqi Feng1
1Department of Biochemistry and Molecular Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Abstract:
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major threat to human health. As a unique putative protein of SARS-CoV-2, the N-terminus of ORF10 can be recognized by ZYG11B, a substrate receptor of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we elucidated recognition mechanism of ORF10 N-terminus by ZYG11B through presenting the crystal structure of ZYG11B bound to ORF10 N-terminal peptide. Our work expands the current understanding of ORF10 interaction with ZYG11B, and may also inspire the development of novel therapies for COVID-19.
Insights
Researchers elucidated how the SARS-CoV-2 ORF10 protein N-terminus interacts with ZYG11B, a key component of the CRL2 ubiquitin ligase. This finding advances understanding of viral protein recognition and may aid in developing new COVID-19 therapies.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a significant global health threat.
- The SARS-CoV-2 ORF10 protein's N-terminus is recognized by ZYG11B, a substrate receptor for the Cullin 2-RING E3 ubiquitin ligase (CRL2) complex.
Purpose of the Study:
- To elucidate the molecular mechanism by which ZYG11B recognizes the N-terminus of the SARS-CoV-2 ORF10 protein.
- To provide structural insights into the ZYG11B-ORF10 interaction.
Main Methods:
- X-ray crystallography was employed to determine the structure of ZYG11B bound to an ORF10 N-terminal peptide.
- Structural analysis of the ZYG11B-ORF10 complex.
Main Results:
- The crystal structure of ZYG11B in complex with the ORF10 N-terminal peptide was successfully determined.
- Detailed structural information on the recognition interface between ZYG11B and ORF10 was obtained.
Conclusions:
- The study provides a structural basis for the recognition of the SARS-CoV-2 ORF10 N-terminus by ZYG11B.
- Understanding this interaction expands knowledge of SARS-CoV-2 protein function and offers potential avenues for novel COVID-19 therapeutic strategies.
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