An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model.
An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model.
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DOI：
10.1016/j.jmb.2009.04.031
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发表时间：
2009-06-26
影响因子：
5.6
通讯作者：
Matsuo, Hiroshi
中科院分区：
文献类型：
--
作者：
Harjes, Elena;Gross, Phillip J.;Chen, Kuan-Ming;Lu, Yongjian;Shindo, Keisuke;Nowarski, Roni;Gross, John D.;Kotler, Moshe;Harris, Reuben S.;Matsuo, Hiroshi
人APOBEC 3G（A3 G）属于多核苷酸胞苷脱氨酶家族。该家族包括APOBEC 1和AID，它们分别编辑APOB mRNA和抗体基因DNA。A3 G将单链DNA中的胞苷脱氨为尿苷，并抑制HIV-1、其他逆转录病毒和逆转录转座子的复制。虽然A3 G催化的DNA脱氨作用的机制已经在遗传学和生物化学上进行了研究，但原子细节才刚刚开始出现。在这里，我们比较了两个A3 G催化结构域构建体的DNA胞苷脱氨酶活性和NMR结构。较长的A3 G191 -384蛋白比较短的A3 G198 -384变体活性高得多。较长的结构具有α1螺旋（残基201-206），这在较短的蛋白质中不明显，并且它通过与疏水核心结构（β1，β3，α5和α6）的相互作用而有助于催化活性。两种A3 G催化结构域溶液结构都具有不连续的β2区，其明显不同于另一个家族成员APOBEC 2的连续β2链。此外，较长的A3 G191 -384结构揭示了部分N-末端假催化结构域，包括结构域间接头和一些最后的α-螺旋。这些结构化的残基（191-196）通过提供N-末端假催化结构域和新的C-末端催化结构域结构之间的物理重叠而实现了新的全长A3 G模型。与预测相反，这种结构约束模型表明，这两个结构域由结构化残基束缚，并且N-和C-末端β2区域彼此距离太远，无法参与这种相互作用。
Human APOBEC3G (A3G) belongs to a family of polynucleotide cytidine deaminases. This family includes APOBEC1 and AID, which edit APOB mRNA and antibody gene DNA, respectively. A3G deaminates cytidines to uridines in single-strand DNA and inhibits the replication of HIV-1, other retroviruses and retrotransposons. Although the mechanism of A3G-catalyzed DNA deamination has been investigated genetically and biochemically, atomic details are just starting to emerge. Here, we compare the DNA cytidine deaminase activities and NMR structures of two A3G catalytic domain constructs. The longer A3G191-384 protein is considerably more active than the shorter A3G198-384 variant. The longer structure has an α1 helix (residues 201–206) that was not apparent in the shorter protein and it contributes to catalytic activity through interactions with hydrophobic core structures (β1, β3, α5 and α6). Both A3G catalytic domain solution structures have a discontinuous β2 region that is clearly different than the continuous β2 strand of another family member APOBEC2. In addition, the longer A3G191-384 structure revealed part of the N-terminal pseudo-catalytic domain including the inter-domain linker and some of the last α-helix. These structured residues (191–196) enabled a novel full-length A3G model by providing physical overlap between the N-terminal pseudo-catalytic domain and the new C-terminal catalytic domain structure. Contrary to predictions, this structurally constrained model suggested that the two domains are tethered by structured residues and that the N- and C-terminal β2 regions are too distant from one another to participate in this interaction.
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影响因子：
3.9
作者：
CARTER, CW
通讯作者：
CARTER, CW
影响因子：
16
作者：
Harris, RS;Petersen-Mahrt, SK;Neuberger, MS
通讯作者：
Neuberger, MS
影响因子：
64.8
作者：
Holden, Lauren G.;Prochnow, Courtney;Chang, Y. Paul;Bransteitter, Ronda;Chelico, Linda;Sen, Udayaditya;Stevens, Raymond C.;Goodman, Myron F.;Chen, Xiaojiang S.
通讯作者：
Chen, Xiaojiang S.
影响因子：
3.5
作者：
Chen, Kuan-Ming;Martemyanova, Natalia;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
64.8
作者：
Chiu, YL;Soros, VB;Greene, WC
通讯作者：
Greene, WC