Cardone Giovanni, Purdy John G, Cheng Naiqian, Craven Rebecca C, Steven Alasdair C
Laboratory of Structural Biology, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature. 2009 Feb 5;457(7230):694-8. doi: 10.1038/nature07724.
For a retrovirus such as HIV to be infectious, a properly formed capsid is needed; however, unusually among viruses, retrovirus capsids are highly variable in structure. According to the fullerene conjecture, they are composed of hexamers and pentamers of capsid protein (CA), with the shape of a capsid varying according to how the twelve pentamers are distributed and its size depending on the number of hexamers. Hexamers have been studied in planar and tubular arrays, but the predicted pentamers have not been observed. Here we report cryo-electron microscopic analyses of two in-vitro-assembled capsids of Rous sarcoma virus. Both are icosahedrally symmetric: one is composed of 12 pentamers, and the other of 12 pentamers and 20 hexamers. Fitting of atomic models of the two CA domains into the reconstructions shows three distinct inter-subunit interactions. These observations substantiate the fullerene conjecture, show how pentamers are accommodated at vertices, support the inference that nucleation is a crucial morphologic determinant, and imply that electrostatic interactions govern the differential assembly of pentamers and hexamers.
对于像HIV这样的逆转录病毒而言，要具有传染性就需要一个结构正常的衣壳；然而，逆转录病毒的衣壳在病毒中异乎寻常地具有高度可变的结构。根据富勒烯猜想，它们由衣壳蛋白（CA）的六聚体和五聚体组成，衣壳的形状根据十二个五聚体的分布方式而变化，其大小则取决于六聚体的数量。六聚体已在平面和管状阵列中得到研究，但预测的五聚体尚未被观察到。在此，我们报告了对劳氏肉瘤病毒两种体外组装衣壳的冷冻电子显微镜分析。两者均为二十面体对称：一个由12个五聚体组成，另一个由12个五聚体和20个六聚体组成。将两个CA结构域的原子模型拟合到重建结构中显示出三种不同的亚基间相互作用。这些观察结果证实了富勒烯猜想，展示了五聚体如何在顶点处容纳，支持了成核是关键形态决定因素的推断，并暗示静电相互作用控制着五聚体和六聚体的差异组装。
