Competitive inhibition of lysine acetyltransferase 2B by a small motif of the adenoviral oncoprotein E1A
Competitive inhibition of lysine acetyltransferase 2B by a small motif of the adenoviral oncoprotein E1A
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DOI：
10.1074/jbc.m115.697300
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Aidong Han
中科院分区：
文献类型：
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作者：
Shasha shi;Ke Liu;Yanheng Chen;Shijun Zhang;Juanyu Lin;Chenfang Gong;Quanwen Jin;Xiang-Jiao Yang;Ruichuan Chen;Zhiliang Ji;Aidong Han
The adenovirus early region 1A (E1A) oncoprotein hijacks host cells via direct interactions with many key cellular proteins, such as KAT2B, also known as PCAF. E1A binds the histone acetyltransferase (HAT) domain of KAT2B to repress its transcriptional activation. However, the molecular mechanism by which how E1A inhibits the HAT activity is not known. Here we demonstrate that a short and relatively conserved N-terminal Motif (cNM) in the intrinsically disordered E1A protein is crucial for the KAT2B interaction, and inhibits its HAT activity through a direct competition with acetyl-CoA, but not its substrate histone H3. Molecular modeling together with a series of mutagenesis experiments suggests that the major helix of E1A cNM binds to a surface of the acetyl-CoA pocket of the KAT2B HAT domain. Moreover, transient expression of the cNM peptide is sufficient to inhibit KAT2B specific H3 acetylation H3K14ac in vivo. Together, our data define an essential motif cNM in N-terminal E1A as an acetyl-CoA entry blocker that directly associates with the entrance of acetyl-CoA binding pocket to block the HAT domain access to its cofactor.
