7CI3

The crystal structure of the SARS-CoV-2 ORF7a ectodomain

Summary for 7CI3

• Entry DOI: 10.2210/pdb7ci3/pdb
• Descriptor: Orf7a protein (2 entities in total)
• Functional Keywords: ig-like fold, type-i transmembrane protein, er membrane, accessory protein, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 9574.88

Authors

Zhou, Z.,Zhou, Z.,Chen, S. (deposition date: 2020-07-07, release date: 2021-03-03, Last modification date: 2024-11-06)

Primary citation

Zhou, Z.,Huang, C.,Zhou, Z.,Huang, Z.,Su, L.,Kang, S.,Chen, X.,Chen, Q.,He, S.,Rong, X.,Xiao, F.,Chen, J.,Chen, S.
Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14 + monocytes.
Iscience, 24:102187-102187, 2021

PubMed Abstract: Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14 monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14 monocytes triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.

PubMed: 33615195
DOI: 10.1016/j.isci.2021.102187

Experimental method

X-RAY DIFFRACTION (2.2 Å)