8T5P

SARS-CoV-2 ORF3a peptide in complex with TRAF3 TRAF domain

8T5P の概要

• エントリーDOI: 10.2210/pdb8t5p/pdb
• 分子名称: TNF receptor-associated factor 3, ORF3a protein (3 entities in total)
• 機能のキーワード: signaling protein-viral protein complex, signaling protein/viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 132542.53

構造登録者

Busscher, B.M.,Xiao, T.S. (登録日: 2023-06-14, 公開日: 2023-11-29, 最終更新日: 2023-12-06)

主引用文献

Busscher, B.M.,Befekadu, H.B.,Liu, Z.,Xiao, T.S.
SARS-CoV-2 ORF3a-Mediated NF-kappa B Activation Is Not Dependent on TRAF-Binding Sequence.
Viruses, 15:-, 2023

PubMed Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus Disease 2019 (COVID-19). Excessive inflammation is a hallmark of severe COVID-19, and several proteins encoded in the SARS-CoV-2 genome are capable of stimulating inflammatory pathways. Among these, the accessory protein open reading frame 3a (ORF3a) has been implicated in COVID-19 pathology. Here we investigated the roles of ORF3a in binding to TNF receptor-associated factor (TRAF) proteins and inducing nuclear factor kappa B (NF-κB) activation. X-ray crystallography and a fluorescence polarization assay revealed low-affinity binding between an ORF3a N-terminal peptide and TRAFs, and a dual-luciferase assay demonstrated NF-κB activation by ORF3a. Nonetheless, mutation of the N-terminal TRAF-binding sequence PIQAS in ORF3a did not significantly diminish NF-κB activation in our assay. Our results thus suggest that the SARS-CoV-2 protein may activate NF-κB through alternative mechanisms.

PubMed: 38005906
DOI: 10.3390/v15112229

実験手法

X-RAY DIFFRACTION (2.5 Å)