8T5Q

SARS-CoV-2 ORF3a peptide in complex with TRAF2 TRAF domain

Summary for 8T5Q

• Entry DOI: 10.2210/pdb8t5q/pdb
• Descriptor: TNF receptor-associated factor 2, ORF3a protein, TETRAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: signaling protein-viral protein complex, signaling protein/viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 129905.57

Authors

Busscher, B.M.,Xiao, T.S. (deposition date: 2023-06-14, release date: 2023-11-29, Last modification date: 2023-12-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)