RNA helicase module in an acetyltransferase that modifies a specific tRNA anticodon

RNA helicase module in an acetyltransferase that modifies a specific tRNA anticodon
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DOI:
10.1038/emboj.2009.69
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发表时间:
2009-05-06
期刊:
影响因子:
11.4
通讯作者:
Tanaka, Isao
Tanaka, Isao
中科院分区:
生物学1区
文献类型:
--
作者:
Chimnaronk, Sarin;Suzuki, Tateki;Tanaka, Isao

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转移 RNA 反密码子中的转录后 RNA 修饰常常有助于蛋白质合成的高保真度。在真细菌中,两种基因组编码的转移 RNA (tRNA) 物种具有与反密码子相同的 CAU 序列,它们通过摆动位置处的修饰胞苷来区分。延伸子 tRNA(Met) 在摆动碱基处接受乙酰基部分,形成 N-4-乙酰胞苷 (ac(4)C):固有修饰通过加强 C-G 碱基对相互作用确保 AUG 密码子的精确解码,同时防止近同源 AUA 密码子的误读。我们以 2.35 埃的分辨率确定了来自大肠杆菌的 tRNA(Met) 胞苷乙酰转移酶 (TmcA) 与两种天然配体乙酰辅酶 A 和 ADP 复合的晶体结构。该结构出人意料地揭示了一个与 GCN5 相关的 N-乙酰转移酶 (GNAT) 折叠融合的特殊 RNA 解旋酶模块,它们密切地交叉相互作用。结合生化证据,我们进一步揭示了乙酰辅酶A作为酶激活开关的功能,并提出由ATP水解驱动的RNA解旋酶马达用于将摆动碱基传递到GNAT结构域的活性中心。 EMBO 杂志 (2009) 28, 1362-1373。 doi:10.1038/emboj.2009.69; 2009 年 3 月 26 日在线发布
Post-transcriptional RNA modifications in the anticodon of transfer RNAs frequently contribute to the high fidelity of protein synthesis. In eubacteria, two genome-encoded transfer RNA (tRNA) species bear the same CAU sequence as the anticodons, which are differentiated by modified cytidines at the wobble positions. The elongator tRNA(Met) accepts an acetyl moiety at the wobble base to form N-4-acetylcytidine (ac(4)C): an inherent modification ensures precise decoding of the AUG codon by strengthening C-G base-pair interaction and concurrently preventing misreading of the near cognate AUA codon. We have determined the crystal structure of tRNA(Met) cytidine acetyl-transferase (TmcA) from Escherichia coli complexed with two natural ligands, acetyl-CoA and ADP, at 2.35 angstrom resolution. The structure unexpectedly reveals an idiosyncratic RNA helicase module fused with a GCN5-related N-acetyltransferase (GNAT) fold, which intimately cross-interact. Taken together with the biochemical evidence, we further unravelled the function of acetyl-CoA as an enzyme-activating switch, and propose that an RNA helicase motor driven by ATP hydrolysis is used to deliver the wobble base to the active centre of the GNAT domain. The EMBO Journal (2009) 28, 1362-1373. doi: 10.1038/emboj.2009.69; Published online 26 March 2009