Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications

被引：185

作者：

Holden, Lauren G. ^{[1
]}

Prochnow, Courtney ^{[1
]}

Chang, Y. Paul ^{[1
]}

Bransteitter, Ronda ^{[1
]}

Chelico, Linda ^{[1
]}

Sen, Udayaditya ^{[1
]}

Stevens, Raymond C. ^{[2
]}

Goodman, Myron F. ^{[1
]}

Chen, Xiaojiang S. ^{[1
]}

机构：

[1] Univ So Calif, Los Angeles, CA 90089 USA

[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

来源：

NATURE | 2008年 / 456卷 / 7218期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nature07357

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The APOBEC family members are involved in diverse biological functions. APOBEC3G restricts the replication of human immunodeficiency virus (HIV), hepatitis B virus and retroelements by cytidine deamination on single- stranded DNA or by RNA binding(1-4). Here we report the high- resolution crystal structure of the carboxy- terminal deaminase domain of APOBEC3G (APOBEC3G-CD2) purified from Escherichia coli. The APOBEC3G-CD2 structure has a five- stranded beta- sheet core that is common to all known deaminase structures and closely resembles the structure of another APOBEC protein, APOBEC2 ( ref. 5). A comparison of APOBEC3G-CD2 with other deaminase structures shows a structural conservation of the active- site loops that are directly involved in substrate binding. In the X- ray structure, these APOBEC3G active- site loops form a continuous 'substrate groove' around the active centre. The orientation of this putative substrate groove differs markedly ( by 90 degrees) from the groove predicted by the NMR structure(6). We have introduced mutations around the groove, and have identified residues involved in substrate specificity, single- stranded DNA binding and deaminase activity. These results provide a basis for understanding the underlying mechanisms of substrate specificity for the APOBEC family.

引用

页码：121 / U13

页数：5

共 15 条

[1] Increased dNTP binding affinity reveals a nonprocessive role for Escherichia coli β clamp with DNA polymerase IV [J].