7CI3

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

7CI3 の概要

• エントリーDOI: 10.2210/pdb7ci3/pdb
• 分子名称: Orf7a protein (2 entities in total)
• 機能のキーワード: ig-like fold, type-i transmembrane protein, er membrane, accessory protein, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9574.88

構造登録者

Zhou, Z.,Zhou, Z.,Chen, S. (登録日: 2020-07-07, 公開日: 2021-03-03, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)