The Wolbachia cytoplasmic incompatibility enzyme CidB targets nuclear import and protamine-histone exchange factors
The Wolbachia cytoplasmic incompatibility enzyme CidB targets nuclear import and protamine-histone exchange factors
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DOI：
10.7554/elife.50026
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发表时间：
2019-11-27
期刊：
影响因子：
7.7
通讯作者：
Hochstrasser, Mark
中科院分区：
文献类型：
--
作者：
Beckmann, John Frederick;Sharma, Gagan Deep;Hochstrasser, Mark
细胞内沃尔巴克氏体细菌操纵节肢动物繁殖，以促进其自身的遗传。最普遍的机制，细胞质不相容性（CI），可追溯到沃尔巴克氏体去泛素化酶，CidB和CidA。CidB具有毒素的性质，而CidA结合CidB并拯救胚胎活力。CidB对酵母也是有毒的，其中我们鉴定了宿主效应和高拷贝毒性抑制剂。最强的抑制剂是核转运蛋白-α，一种核输入受体;这需要核定位信号结合。使用底物捕获催化突变体CidB（星星）对果蝇提取物进行的蛋白质相互作用筛选也鉴定出了karyopherina; P32鱼精蛋白-组蛋白交换因子也结合在一起。当CidB（星星）与CidA结合时，这些宿主蛋白相互作用消失。这些协会将CidB在合子男性原核CI缺陷首次出现。在雌性果蝇中过表达karyopherin-alpha、P32或CidA可抑制CI。我们建议，CidB的目标核蛋白进口和鱼精蛋白-组蛋白交换和CidA拯救胚胎限制CidB进入其目标。
Intracellular Wolbachia bacteria manipulate arthropod reproduction to promote their own inheritance. The most prevalent mechanism, cytoplasmic incompatibility (CI), traces to a Wolbachia deubiquitylase, CidB, and CidA. CidB has properties of a toxin, while CidA binds CidB and rescues embryonic viability. CidB is also toxic to yeast where we identified both host effects and high-copy suppressors of toxicity. The strongest suppressor was karyopherin-alpha, a nuclear-import receptor; this required nuclear localization-signal binding. A protein-interaction screen of Drosophila extracts using a substrate-trapping catalytic mutant, CidB(star), also identified karyopherina; the P32 protamine-histone exchange factor bound as well. When CidB(star) bound CidA, these host protein interactions disappeared. These associations would place CidB at the zygotic male pronucleus where CI defects first manifest. Overexpression of karyopherin-alpha, P32, or CidA in female flies suppressed CI. We propose that CidB targets nuclear-protein import and protamine-histone exchange and that CidA rescues embryos by restricting CidB access to its targets.