7TUQ

Crystal structure of BRD4 bromodomain 1 in complex with monoacetylated SARS-CoV-2 E

Summary for 7TUQ

• Entry DOI: 10.2210/pdb7tuq/pdb
• Descriptor: Bromodomain-containing protein 4, Envelope small membrane protein (3 entities in total)
• Functional Keywords: brd4, bromodomain, sars-cov-2, covid, envelope protein, e protein, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 33872.91

Authors

Vann, K.R.,Kutateladze, T.G. (deposition date: 2022-02-03, release date: 2022-07-06, Last modification date: 2024-11-13)

Primary citation

Vann, K.R.,Acharya, A.,Jang, S.M.,Lachance, C.,Zandian, M.,Holt, T.A.,Smith, A.L.,Pandey, K.,Durden, D.L.,El-Gamal, D.,Cote, J.,Byrareddy, S.N.,Kutateladze, T.G.
Binding of the SARS-CoV-2 envelope E protein to human BRD4 is essential for infection.
Structure, 30:1224-, 2022

PubMed Abstract: Emerging new variants of SARS-CoV-2 and inevitable acquired drug resistance call for the continued search of new pharmacological targets to fight the potentially fatal infection. Here, we describe the mechanisms by which the E protein of SARS-CoV-2 hijacks the human transcriptional regulator BRD4. We found that SARS-CoV-2 E is acetylated in vivo and co-immunoprecipitates with BRD4 in human cells. Bromodomains (BDs) of BRD4 bind to the C-terminus of the E protein, acetylated by human acetyltransferase p300, whereas the ET domain of BRD4 recognizes the unmodified motif of the E protein. Inhibitors of BRD4 BDs, JQ1 or OTX015, decrease SARS-CoV-2 infectivity in lung bronchial epithelial cells, indicating that the acetyllysine binding function of BDs is necessary for the virus fitness and that BRD4 represents a potential anti-COVID-19 target. Our findings provide insight into molecular mechanisms that contribute to SARS-CoV-2 pathogenesis and shed light on a new strategy to block SARS-CoV-2 infection.

PubMed: 35716662
DOI: 10.1016/j.str.2022.05.020

Experimental method

X-RAY DIFFRACTION (2.68 Å)