The crystal structure of the Zβ domain of the RNA-editing enzyme ADAR1 reveals distinct conserved surfaces among Z-domains
The crystal structure of the Zβ domain of the RNA-editing enzyme ADAR1 reveals distinct conserved surfaces among Z-domains
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DOI：
10.1016/j.jmb.2005.06.028
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发表时间：
2005-08-19
影响因子：
5.6
通讯作者：
Rich, A
中科院分区：
文献类型：
--
作者：
Athanasiadis, A;Placido, D;Rich, A
Z α结构域代表有翼螺旋-转角-螺旋（HTH）结构域家族的一个不断增长的亚家族，其成员共享特异性结合Z-DNA和/或Z-RNA的显著能力。它们仅在参与干扰素应答的蛋白质中被发现，虽然它们在决定痘病毒致病性方面的重要性已被证明，但它们的实际靶点和生物学作用仍不清楚。含有Z α结构域的细胞蛋白带有称为Z β的第二个同源结构域，其似乎缺乏结合左手核酸的能力。在这里，我们提出的Z β结构域的人双链RNA腺苷脱氨酶ADAR 1在0.97 A，确定通过单一的同晶置换，包括异常散射。Z β通过添加C-末端螺旋来维持翼形HTH折叠。在Z β表面上的Z β保守分布图揭示了部分由末端螺旋4形成的新的保守表面，其参与金属结合和二聚化并且不存在于Z α结构域。我们的研究结果表明，即使在相同的蛋白质中，两个折叠相似的结构域也可能进化成不同的功能实体。(c)2005爱思唯尔有限公司保留所有权利。
The Z alpha domains represent a growing subfamily of the winged helix-turn-helix (HTH) domain family whose members share a remarkable ability to bind specifically to Z-DNA and/or Z-RNA. They have been found exclusively in proteins involved in interferon response and, while their importance in determining pox viral pathogenicity has been demonstrated, their actual target and biological role remain obscure. Cellular proteins containing Z alpha domains bear a second homologous domain termed Z beta which appears to lack the ability to bind left-handed nucleic acids. Here, we present the crystal structure of the Z beta domain from the human double-stranded RNA adenosine deaminase ADAR1 at 0.97 A, determined by single isomorphous replacement including anomalous scattering. Z beta maintains a winged-HTH fold with the addition of a C-terminal helix. Mapping of the Z beta conservation profile on the Z beta surface reveals a new conserved surface formed partly by the terminal helix 4, involved in metal binding and dimerization and absent from Z alpha domains. Our results show how two domains similar in fold may have evolved into different functional entities even in the context of the same protein. (c) 2005 Elsevier Ltd. All rights reserved.