Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks.
Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks.
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通过冷冻电镜研究人类腺病毒的原子结构揭示蛋白质网络之间的相互作用
DOI：
10.1126/science.1187433
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发表时间：
2010-08-27
期刊：
影响因子：
--
通讯作者：
Zhou ZH
中科院分区：
文献类型：
--
作者：
Liu H;Jin L;Koh SB;Atanasov I;Schein S;Wu L;Zhou ZH
人腺病毒可能是人类急性感染的常见原因，但它们也可以用作疫苗和治疗基因转移的载体。由于缺乏高分辨率的结构信息，安全的腺病毒载体的合理工程化受到阻碍。现在有两篇论文使用互补技术描述了人类腺病毒的结构。Reddy等人（第1071页;参见Harrison的Perspective）已经确定了3.5埃分辨率的晶体结构，而Liu等人（第1038页;参见Harrison的Perspective）通过电子显微镜将结构解析到3.6埃分辨率。这些结构一起提供了对病毒组装、稳定化和细胞进入机制的见解。高分辨率结构为优化腺病毒作为疫苗和基因治疗载体提供了基础。复杂病毒的构建可能涉及组装元件的层次结构。在这里，我们报告的结构，整个人类腺病毒病毒粒子在3.6埃的分辨率，冷冻电子显微镜（cryo-EM），揭示在原位原子模型的三个次要衣壳蛋白（IIIa，VIII和IX），扩展（五邻体基地和六邻体）主要衣壳蛋白，和三个蛋白质-蛋白质网络内的相互作用。一个网络是由蛋白IIIa介导的顶点，在六组（GOS）瓦片-一个五邻体基地和它的五个周围的六邻体。另一种是由绳索（蛋白质IX）介导的，绳索将六邻体捆绑在一起形成九组（GON）瓦片并将GON与GON结合。第三种由IIIa和VIII介导，将每个GOS与周围的五个GON结合。优化用于癌症和基因治疗的腺病毒可以针对这些网络。
Human Adenovirus Structures Human adenoviruses may be a common cause of acute infections in humans, but they can also be used as vectors for vaccine and therapeutic gene transfer. Rational engineering of safe adenovirus vectors has been hampered by a lack of high-resolution structural information. Two papers now describe the structure of human adenovirus using complementary techniques. Reddy et al. (p. 1071; see the Perspective by Harrison) have determined the crystal structure at 3.5 angstrom resolution, while Liu et al. (p. 1038; see the Perspective by Harrison) solved the structure to 3.6 angstrom resolution by electron microscopy. Together the structures provide insights into viral assembly, stabilization, and cell entry mechanisms. High-resolution structures provide a basis for optimizing adenovirus as a vaccine and gene-therapy vector. Construction of a complex virus may involve a hierarchy of assembly elements. Here, we report the structure of the whole human adenovirus virion at 3.6 angstroms resolution by cryo–electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of the (penton base and hexon) major capsid proteins, and interactions within three protein-protein networks. One network is mediated by protein IIIa at the vertices, within group-of-six (GOS) tiles—a penton base and its five surrounding hexons. Another is mediated by ropes (protein IX) that lash hexons together to form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for cancer and gene therapy could target these networks.
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影响因子：
5.6
作者：
Perez-Berna, Ana J.;Marabini, Roberto;Scheres, Sjors H. W.;Menendez-Conejero, Rosa;Dmitriev, Igor P.;Curiel, David T.;Mangel, Walter F.;Flint, S. Jane;San Martin, Carmen
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影响因子：
11.4
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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