CAEV Vif Hijacks ElonginB/C, CYPA and Cullin5 to Assemble the E3 Ubiquitin Ligase Complex Stepwise to Degrade oaA3Z2-Z3
CAEV Vif Hijacks ElonginB/C, CYPA and Cullin5 to Assemble the E3 Ubiquitin Ligase Complex Stepwise to Degrade oaA3Z2-Z3
复制标题
CAEV Vif 劫持 ElonginB/C、CYPA 和 Cullin5 逐步组装 E3 泛素连接酶复合物以降解 oaA3Z2-Z3
DOI：
10.3389/fmicb.2019.00565
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Zhang Wenyan
中科院分区：
文献类型：
--
作者：
Zhao Zhilei;Li Zhaolong;Huan Chen;Wang Hong;Su Xing;Zhang Wenyan
山羊关节炎脑炎病毒（CAEV）是一种慢病毒，可引起绵羊和山羊多系统慢性疾病。它对Vif进行编码，通过诱导oaA3Z2-Z3的降解来抵消oaA3Z2-Z3的限制。然而，CAEV Vif和OaA3Z2-Z3之间相互作用的机制尚未被阐明。在这里，我们确定了被CAEV Vif劫持的细胞因子伸长b /C、CYPA和Cullin5，以及CAEV Vif降解oaA3Z2-Z3所需的几个功能域。此外，我们确定CAEV Vif通过SLE基序（170SLE172）逐步组装E3泛素连接酶来招募ElonginB/C， P21位点和锌指基序（C132-C134-C154-C157）来招募CYPA，以及疏水结构域（141IR142）来招募Cullin5。这种CAEV Vif介导的E3连接酶触发oaA3Z2-Z3的蛋白酶体降解，oaA3Z2-Z3通过残基Y39和L44直接结合CAEV Vif。特别是，CYPA在调节连接酶组装过程中发挥了重要作用，这与CBF-β类似，CBF-β是HIV-1和siv介导的E3连接酶的基本调节剂，这表明来自不同慢病毒亚群的Vifs需要对细胞伴侣进行模块化保护和谱系特异性偏好。综上所述，这些发现提供了关于CAEV Vif功能的重要见解，并加深了我们对慢病毒与其宿主之间军备竞赛的理解。
Caprine arthritis encephalitis virus (CAEV) is a lentivirus that causes multisystemic chronic disorders in sheep and goats. It encodes Vif to counteract the restriction of Ovis aries A3Z2-Z3 (oaA3Z2-Z3) by inducing their degradation. Nevertheless, the mechanisms underlying the interplay between CAEV Vif and OaA3Z2-Z3 have yet to be elucidated. Here, we identified the cellular factors ElonginB/C, CYPA and Cullin5 as being hijacked by CAEV Vif as well as several functional domains of CAEV Vif required for degrading oaA3Z2-Z3. Moreover, we determined that CAEV Vif assembled E3 ubiquitin ligase stepwise via its SLE motif (170SLE172) to recruit ElonginB/C, the P21 site and the zinc finger motif (C132-C134-C154-C157) to recruit CYPA, as well as the hydrophobic domain (141IR142) to recruit Cullin5. And this CAEV Vif-mediated E3 ligase triggers the proteasomal degradation of oaA3Z2-Z3, which directly bind CAEV Vif through residues Y39 and L44. In particular, CYPA played an essential role in the process to regulate ligase assembly, which was analogous to CBF-β, the essential regulator for HIV-1 and SIV-mediated E3 ligase, indicating that there is a modular conservation and lineage-specific preference for cellular partners required by Vifs from different subgroups of lentiviruses. Taken together, these findings provide important insights regarding the CAEV Vif function and deepen our understanding of the arms race between the lentiviruses and their hosts.
登录
查看更多内容
影响因子：
3
作者：
Wendl MC
通讯作者：
Wendl MC
针对VIF的HIV-1治疗策略的结构见解。
影响因子：
13.8
作者：
Salter JD;Morales GA;Smith HC
通讯作者：
Smith HC
影响因子：
14.9
作者：
Jonsson, Stefan R.;Hache, Guylaine;Stenglein, Mark D.;Fahrenkrug, Scott C.;Andresdottir, Valgerdur;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
5.4
作者：
LaRue, Rebecca S.;Lengyel, Joy;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
64.8
作者：
Jaeger, Stefanie;Kim, Dong Young;Hultquist, Judd F.;Shindo, Keisuke;LaRue, Rebecca S.;Kwon, Eunju;Li, Ming;Anderson, Brett D.;Yen, Linda;Stanley, David;Mahon, Cathal;Kane, Joshua;Franks-Skiba, Kathy;Cimermancic, Peter;Burlingame, Alma;Sali, Andrej;Craik, Charles S.;Harris, Reuben S.;Gross, John D.;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.