Structure and architecture of immature and mature murine leukemia virus capsids
Structure and architecture of immature and mature murine leukemia virus capsids
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DOI：
10.1073/pnas.1811580115
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发表时间：
2018-12-11
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：
Qu, Kun;Glass, Barbel;Briggs, John A. G.
逆转录病毒以不成熟的形式从受感染的细胞中组装和出芽，并且需要蛋白水解成熟以获得感染性。Gag多聚蛋白的CA（衣壳）结构域在未成熟病毒体中组装成蛋白质晶格作为截短的球体。Gag的蛋白水解裂解诱导戏剧性的结构重排;裂解的CA的子集随后组装成成熟的核心，其结构在逆转录病毒中各不相同。鼠白血病病毒（MLV）是典型的γ-逆转录病毒，并作为逆转录病毒载体的基础，但MLV CA层的结构是未知的。在这里，我们结合了X射线晶体学与冷冻电子断层扫描，以确定真正的病毒颗粒内的未成熟和成熟的MLV CA层的结构。这揭示了与成熟相关的结构变化，并通过与HIV-1的比较，揭示了保守和可变的特征。与HIV-1相反，大多数MLV CA用于成熟核心的组装，其采用可变的多层形态并且不形成封闭结构。与HIV-1不同，未成熟MLV CA层中的蛋白质-蛋白质界面与成熟CA层中的蛋白质-蛋白质界面之间存在相似性，并且MLV的结构成熟可以通过结构域旋转来实现，该结构域旋转在很大程度上维持六聚体相互作用。然而，成熟时的戏剧性的架构变化表明，成熟的核心增长需要广泛的拆卸和重新组装。核心形态表明，CA片层中的基因组包裹可能足以在细胞进入期间保护MLV核糖核蛋白。
Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA subsequently assembles into the mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is the prototypical gamma-retrovirus and serves as the basis of retroviral vectors, but the structure of the MLV CA layer is unknown. Here we have combined X-ray crystallography with cryoelectron tomography to determine the structures of immature and mature MLV CA layers within authentic viral particles. This reveals the structural changes associated with maturation, and, by comparison with HIV-1, uncovers conserved and variable features. In contrast to HIV-1, most MLV CA is used for assembly of the mature core, which adopts variable, multilayered morphologies and does not form a closed structure. Unlike in HIV-1, there is similarity between protein-protein interfaces in the immature MLV CA layer and those in the mature CA layer, and structural maturation of MLV could be achieved through domain rotations that largely maintain hexameric interactions. Nevertheless, the dramatic architectural change on maturation indicates that extensive disassembly and reassembly are required for mature core growth. The core morphology suggests that wrapping of the genome in CA sheets may be sufficient to protect the MLV ribonucleoprotein during cell entry.