Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif

被引：184

作者：

Guo, Yingying ^{[1
]}

Dong, Liyong ^{[1
]}

Qiu, Xiaolin ^{[1
]}

Wang, Yishu ^{[1
]}

Zhang, Bailing ^{[1
]}

Liu, Hongnan ^{[1
]}

Yu, You ^{[2
]}

Zang, Yi ^{[1
]}

Yang, Maojun ^{[2
]}

Huang, Zhiwei ^{[1
]}

机构：

[1] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Peoples R China

[2] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China

来源：

NATURE | 2014年 / 505卷 / 7482期

基金：

中国国家自然科学基金;

关键词：

UBIQUITIN LIGASE; SOCS BOX; ENZYME APOBEC3G; PROTEIN; DNA; DEGRADATION; HYPERMUTATION; INFECTION; SOFTWARE; MOTIF;

D O I：

10.1038/nature12884

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defences by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors(1-6); however, the underlying mechanism by which Vif achieves this remains unclear. Here we report a crystal structure of the Vif-CBF-beta-CUL5-ELOB-ELOC complex. The structure reveals that Vif, by means of two domains, organizes formation of the pentameric complex by interacting with CBF-beta, CUL5 and ELOC. The larger domain (alpha/beta domain) of Vif binds to the same side of CBF-beta as RUNX1, indicating that Vif and RUNX1 are exclusive for CBF-beta binding. Interactions of the smaller domain (alpha-domain) of Vif with ELOCand CUL5 are cooperative and mimic those of SOCS2 with the latter two proteins. A unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contacts with the other proteins but stabilizes the conformation of the alpha-domain, which may be important for Vif-CUL5 interaction. Together, our data reveal the structural basis for Vif hijacking of the CBF-beta and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs.

引用

页码：229 / +

页数：16

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