Model of the Trimeric Fiber and Its Interactions with the Pentameric Penton Base of Human Adenovirus by Cryo-electron Microscopy
文献类型：期刊论文
| 作者 | Liu, Hongrong1,2,3; Wu, Lily2,4; Zhou, Z. Hong1,2 |
| 刊名 | JOURNAL OF MOLECULAR BIOLOGY
 |
| 出版日期 | 2011-03-11 |
| 卷号 | 406页码:764-774 |
| 关键词 | adenovirus fiber penton base symmetry mismatch cryoEM |
| ISSN号 | 0022-2836 |
| DOI | 10.1016/j.jmb.2010.11.043 |
| 英文摘要 | Adenovirus invades host cells by first binding to host receptors through a trimeric fiber, which contains three domains: a receptor-binding knob domain, a long flexible shaft domain, and a penton base-attachment tail domain. Although the structure of the knob domain associated with a portion of the shaft has been solved by X-ray crystallography, the in situ structure of the fiber in the virion is not known; thus, it remains a mystery how the trimeric fiber attaches to its underlying pentameric penton base. By high-resolution cryo-electron microscopy, we have determined the structure of the human adenovirus type 5 (Ad5) to 3.6-angstrom resolution and have reported the full atomic models for its capsid proteins, but not for the fiber whose density cannot be directly interpreted due to symmetry mismatch with the penton base. Here, we report the determination of the Ad5 fiber structure and its mode of attachment to the pentameric penton base by using an integrative approach of multi-resolution filtering, homology modeling, computational simulation of mismatched symmetries, and fitting of atomic models into cryo-electron microscopy density maps. Our structure reveals that the interactions between the trimeric fiber and the pentameric penton base are mediated by a hydrophobic ring on the top surface of the penton base and three flexible tails inserted into three of the five available grooves formed by neighboring subunits of penton base. These interaction sites provide the molecular basis for the symmetry mismatch and can be targeted for optimizing adenovirus for gene therapy applications. (C) 2010 Elsevier Ltd. All rights reserved. |
| WOS关键词 | SINGLE-PARTICLE RECONSTRUCTIONS ; ANGSTROM RESOLUTION ; CRYSTAL-STRUCTURE ; RECEPTOR ; PROTEIN ; HEXON ; REVEALS ; VISUALIZATION ; INFECTION ; SYMMETRY |
| 资助项目 | National Institutes of Health[GM071940] ; National Institutes of Health[AI069015] ; National Institutes of Health[CA101904] ; National Institutes of Health[1S10RR23057] ; National Natural Scientific Foundations of China[31070663] ; National Natural Scientific Foundations of China[10874144] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000288415900010 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 资助机构 | National Institutes of Health ; National Natural Scientific Foundations of China |
| 源URL | [http://119.78.100.186/handle/113462/34190]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Zhou, Z. Hong |
| 作者单位 | 1.Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA 2.Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA 3.Xiangtan Univ, Inst Modern Phys, Xiangtan 411105, Hunan, Peoples R China 4.Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Inst Mol Med IMED, Los Angeles, CA 90095 USA |
| 推荐引用方式 GB/T 7714 | Liu, Hongrong,Wu, Lily,Zhou, Z. Hong. Model of the Trimeric Fiber and Its Interactions with the Pentameric Penton Base of Human Adenovirus by Cryo-electron Microscopy[J]. JOURNAL OF MOLECULAR BIOLOGY,2011,406:764-774. |
| APA | Liu, Hongrong,Wu, Lily,&Zhou, Z. Hong.(2011).Model of the Trimeric Fiber and Its Interactions with the Pentameric Penton Base of Human Adenovirus by Cryo-electron Microscopy.JOURNAL OF MOLECULAR BIOLOGY,406,764-774. |
| MLA | Liu, Hongrong,et al."Model of the Trimeric Fiber and Its Interactions with the Pentameric Penton Base of Human Adenovirus by Cryo-electron Microscopy".JOURNAL OF MOLECULAR BIOLOGY 406(2011):764-774. |
入库方式： OAI收割
来源：近代物理研究所
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