The molecular organization of cypovirus polyhedra
The molecular organization of cypovirus polyhedra
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DOI：
10.1038/nature05628
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发表时间：
2007-03-01
期刊：
影响因子：
64.8
通讯作者：
Metcalf, Peter
中科院分区：
文献类型：
--
作者：
Coulibaly, Fasseli;Chiu, Elaine;Metcalf, Peter
众所周知，轮状病毒和杆状病毒很难根除，因为病毒颗粒嵌入了被称为多面体(1，2)的微米级蛋白质晶体中。多角体的显著稳定性意味着，这些昆虫病毒像细菌孢子一样，在土壤中保持多年的传染性。多面体在环境中的持久性是蚕茧收成严重损失的原因，但也被用来作为化学杀虫剂的生物替代品来防治害虫(3，4)。尽管自20世纪初以来，多面体已经被广泛地表征(5)，但它们的原子组织仍然难以捉摸(6)。在这里，我们描述了重组和感染性家蚕环状病毒多角体的2埃晶体结构，这些晶体是用从昆虫细胞中纯化的直径5-12微米的晶体确定的。这是迄今用于从头开始X射线蛋白质结构测定的最小晶体(7)。我们发现，多角体是由病毒多角体蛋白的三聚体组成的，含有核苷酸。尽管这些积木的形状让人想起一些衣壳三聚体，但多面体有一个新的折叠，并在体内进化成三维立方晶体，而不是二十面体的壳。多角体蛋白三聚体通过非共价相互作用在多面体中广泛交联，并具有类似于抗原-抗体复合体的精致的分子互补性。由此产生的超稳定和密封的晶体保护病毒颗粒免受环境破坏。这种结构表明，多面体可以作为开发用于生物技术应用的强大和多功能纳米颗粒的基础8，例如微阵列(9)和生物杀虫剂(4)。
Cypoviruses and baculoviruses are notoriously difficult to eradicate because the virus particles are embedded in micrometresized protein crystals called polyhedra(1,2). The remarkable stability of polyhedra means that, like bacterial spores, these insect viruses remain infectious for years in soil. The environmental persistence of polyhedra is the cause of significant losses in silkworm cocoon harvests but has also been exploited against pests in biological alternatives to chemical insecticides(3,4). Although polyhedra have been extensively characterized since the early 1900s(5), their atomic organization remains elusive(6). Here we describe the 2 angstrom crystal structure of both recombinant and infectious silkworm cypovirus polyhedra determined using crystals 5 - 12 micrometres in diameter purified from insect cells. These are the smallest crystals yet used for de novo X-ray protein structure determination(7). We found that polyhedra are made of trimers of the viral polyhedrin protein and contain nucleotides. Although the shape of these building blocks is reminiscent of some capsid trimers, polyhedrin has a new fold and has evolved to assemble in vivo into three-dimensional cubic crystals rather than icosahedral shells. The polyhedrin trimers are extensively cross-linked in polyhedra by non-covalent interactions and pack with an exquisite molecular complementarity similar to that of antigen - antibody complexes. The resulting ultrastable and sealed crystals shield the virus particles from environmental damage. The structure suggests that polyhedra can serve as the basis for the development of robust and versatile nanoparticles for biotechnological applications 8 such as microarrays(9) and biopesticides(4).