7VPG

Crystal structure of the C-terminal tail of SARS-CoV-1 Orf6 complex with human nucleoporin pair Rae1-Nup98

Summary for 7VPG

• Entry DOI: 10.2210/pdb7vpg/pdb
• Descriptor: mRNA export factor, Isoform 3 of Nuclear pore complex protein Nup98-Nup96, ORF6 protein, ... (4 entities in total)
• Functional Keywords: complex, coronavirus, rna nuclear export, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 211368.70

Authors

Li, T.,Guo, H.,Yang, T.,Wen, Y.,Ji, X. (deposition date: 2021-10-17, release date: 2022-01-19, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.49 Å)