Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag
Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag
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DOI：
10.1126/sciadv.aay6354
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发表时间：
2020-01-01
期刊：
影响因子：
13.6
通讯作者：
Taylor, Ian A.
中科院分区：
文献类型：
--
作者：
Cottee, Matthew A.;Letham, Suzanne C.;Taylor, Ian A.
四足动物神经元蛋白ARC和它的果蝇黑腹果蝇同源物dARC1在神经元发育中扮演着重要但不同的角色。两者都被认为起源于古老的Ty3/Gypsy反转录转座子GAG，其新的功能依赖于原始的核酸自组装和封装能力。在这里，我们介绍了dARC1 CA的晶体结构，并研究了dARC1、哺乳动物ARC和循环中逆转录病毒的CA蛋白之间的关系。我们发现，虽然总体结构与正反转录病毒和SpumaretroVirus CA的结构高度相关，但在氨基和羧基末端结构域都有很大的偏离，可能会影响伙伴蛋白的招募和颗粒组装。序列和结构差异的程度表明，Ty3/Gypsy Gag已经在两个不同的场合被剔除，尽管哺乳动物的ARC和dARC1在功能上有相似之处，但在窃取到四足动物和昆虫的基因组后，这些结构经历了不同的适应。
The tetrapod neuronal protein ARC and its Drosophila melanogaster homolog, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag, with their novel function relying on an original capacity for self-assembly and encapsidation of nucleic acids. Here, we present the crystal structure of dARC1 CA and examine the relationship between dARC1, mammalian ARC, and the CA protein of circulating retroviruses. We show that while the overall architecture is highly related to that of orthoretroviral and spumaretroviral CA, there are substantial deviations in both amino-and carboxyl-terminal domains, potentially affecting recruitment of partner proteins and particle assembly. The degree of sequence and structural divergence suggests that Ty3/Gypsy Gag has been exapted on two separate occasions and that, although mammalian ARC and dARC1 share functional similarity, the structures have undergone different adaptations after appropriation into the tetrapod and insect genomes.