Structure of the Ty3/Gypsy retrotransposon capsid and the evolution of retroviruses
Structure of the Ty3/Gypsy retrotransposon capsid and the evolution of retroviruses
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DOI：
10.1073/pnas.1900931116
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发表时间：
2019-05-14
影响因子：
11.1
通讯作者：
Briggs, John A. G.
中科院分区：
文献类型：
--
作者：
Dodonova, Svetlana O.;Prinz, Simone;Briggs, John A. G.
逆转录病毒通过获得包膜功能从长末端重复序列（LTR）逆转录转座子进化而来，随后再入侵宿主基因组。内源性逆转录病毒和LTR逆转录转座子共同代表了动物、植物和真菌基因组的主要组分。来自这些元件的序列已被exapted执行基本的宿主功能，包括胎盘发育，突触通讯和转录调节。它们编码Gag多肽，其衣壳结构域可以寡聚化以形成病毒样颗粒。逆转录病毒衣壳的结构已被广泛描述。它们通过全长Gag的寡聚化组装未成熟的病毒颗粒。Gag的蛋白水解裂解导致成熟的感染性颗粒。相反，LTR反转录转座子衣壳结构数据的缺乏阻碍了我们对其功能和进化关系的理解。在这里，我们报告的衣壳形态和结构的原型吉普赛反转录转座子Ty 3。我们对细胞内未成熟和成熟的Ty 3颗粒进行了电子断层扫描（ET）。我们发现，与逆转录病毒相反，这些病毒在成熟后不会改变大小或形状。冷冻ET和冷冻电子显微镜纯化，未成熟的Ty 3颗粒揭示了一个不规则的富勒烯几何形状先前描述的成熟逆转录病毒核心颗粒和三级和四级排列的衣壳（CA）的C-末端结构域内组装的衣壳是保守的成熟HIV-1。这些发现为研究反转录转座子衣壳提供了结构基础，包括高等生物中驯化的那些。他们表明，通过结构上不同的未成熟衣壳组装是后来的逆转录病毒适应，而成熟组装衣壳的结构在LTR逆转录转座子和逆转录病毒之间是保守的。
Retroviruses evolved from long terminal repeat (LTR) retrotransposons by acquisition of envelope functions, and subsequently reinvaded host genomes. Together, endogenous retroviruses and LTR retrotransposons represent major components of animal, plant, and fungal genomes. Sequences from these elements have been exapted to perform essential host functions, including placental development, synaptic communication, and transcriptional regulation. They encode a Gag polypeptide, the capsid domains of which can oligomerize to form a virus-like particle. The structures of retroviral capsids have been extensively described. They assemble an immature viral particle through oligomerization of full-length Gag. Proteolytic cleavage of Gag results in amature, infectious particle. In contrast, the absence of structural data on LTR retrotransposon capsids hinders our understanding of their function and evolutionary relationships. Here, we report the capsid morphology and structure of the archetypal Gypsy retrotransposon Ty3. We performed electron tomography (ET) of immature and mature Ty3 particles within cells. We found that, in contrast to retroviruses, these do not change size or shape upon maturation. Cryo-ET and cryo-electron microscopy of purified, immature Ty3 particles revealed an irregular fullerene geometry previously described for mature retrovirus core particles and a tertiary and quaternary arrangement of the capsid (CA) C-terminal domain within the assembled capsid that is conserved with mature HIV-1. These findings provide a structural basis for studying retrotransposon capsids, including those domesticated in higher organisms. They suggest that assembly via a structurally distinct immature capsid is a later retroviral adaptation, while the structure of mature assembled capsids is conserved between LTR retrotransposons and retroviruses.