7VPH

Crystal structure of the C-terminal tail of SARS-CoV-2 Orf6 complex with human nucleoporin pair Rae1-Nup98

7VPH の概要

• エントリーDOI: 10.2210/pdb7vph/pdb
• 分子名称: mRNA export factor, Isoform 3 of Nuclear pore complex protein Nup98-Nup96, ORF6 protein, ... (4 entities in total)
• 機能のキーワード: complex, coronavirus, rna nuclear export, protein binding, viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 210683.66

構造登録者

Li, T.,Guo, H.,Yang, T.,Wen, Y.,Ji, X. (登録日: 2021-10-17, 公開日: 2022-01-19, 最終更新日: 2023-11-29)

主引用文献

Li, T.,Wen, Y.,Guo, H.,Yang, T.,Yang, H.,Ji, X.
Molecular Mechanism of SARS-CoVs Orf6 Targeting the Rae1-Nup98 Complex to Compete With mRNA Nuclear Export.
Front Mol Biosci, 8:813248-813248, 2021

PubMed Abstract: The accessory protein Orf6 is uniquely expressed in sarbecoviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is an ongoing pandemic. SARS-CoV-2 Orf6 antagonizes host interferon signaling by inhibition of mRNA nuclear export through its interactions with the ribonucleic acid export 1 (Rae1)-nucleoporin 98 (Nup98) complex. Here, we confirmed the direct tight binding of Orf6 to the Rae1-Nup98 complex, which competitively inhibits RNA binding. We determined the crystal structures of both SARS-CoV-2 and SARS-CoV-1 Orf6 C-termini in complex with the Rae1-Nup98 heterodimer. In each structure, SARS-CoV Orf6 occupies the same potential mRNA-binding groove of the Rae1-Nup98 complex, comparable to the previously reported structures of other viral proteins complexed with Rae1-Nup98, indicating that the Rae1-Nup98 complex is a common target for different viruses to impair the nuclear export pathway. Structural analysis and biochemical studies highlight the critical role of the highly conserved methionine (M58) of SARS-CoVs Orf6. Altogether our data unravel a mechanistic understanding of SARS-CoVs Orf6 targeting the mRNA-binding site of the Rae1-Nup98 complex to compete with the nuclear export of host mRNA, which further emphasizes that Orf6 is a critical virulence factor of SARS-CoVs.

PubMed: 35096974
DOI: 10.3389/fmolb.2021.813248

実験手法

X-RAY DIFFRACTION (2.8 Å)