The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6.
The 8ab protein of SARS-CoV is a group-specific accessory protein, which is lost when the virus was transmitted from animals to humans due to a 29-nucleotide deletion in the ORF8ab region. Here we found that 8ab protein is associated with ER membrane at luminal surface. 8ab protein was found to up-regulate the synthesis of endogenous ER-resident chaperons involved in protein folding through the activation of the transcription factor ATF6, while it showed no effect on the CHOP induction and XBP1 splicing associated with the unfolded protein response (UPR). When ectopically expressed in mammalian cells, 8ab induced the proteolysis of ATF6 and the translocation of its cleaved DNA-binding and transcription-activation domains from the ER to the nucleus. Finally, we showed that 8ab binds to the luminal domain of ATF6. These findings suggest that 8ab could modulate the UPR by activating ATF6 to facilitate protein folding and processing. Thus, the loss of 8ab in SARS-CoV through viral evolution in animals may play a role in its pathogenicity.
Sung
Shu-Chiun
SC
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Chao
Che-Yi
CY
Jeng
King-Song
KS
Yang
Jyh-Yuan
JY
Lai
Michael M C
MM
D051702:Activating Transcription Factor 6 / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D021381:Protein Transport; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D016415:Sequence Alignment; D015854:Up-Regulation; D014709:Vero Cells; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*
D051702:Activating Transcription Factor 6; D054334:Viral Regulatory and Accessory Proteins