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腺病毒蛇腺病毒1纤维头部结构域的晶体结构

Crystal structure of the fibre head domain of the Atadenovirus Snake Adenovirus 1.

作者信息

Singh Abhimanyu K, Menéndez-Conejero Rosa, San Martín Carmen, van Raaij Mark J

机构信息

Departamento de Estructura de Macromoleculas, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, Spain; NanoBiomedicine Initiative, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, Spain.

出版信息

PLoS One. 2014 Dec 8;9(12):e114373. doi: 10.1371/journal.pone.0114373. eCollection 2014.

Abstract

Adenoviruses are non-enveloped icosahedral viruses with trimeric fibre proteins protruding from their vertices. There are five known genera, from which only Mastadenoviruses have been widely studied. Apart from studying adenovirus as a biological model system and with a view to prevent or combat viral infection, there is a major interest in using adenovirus for vaccination, cancer therapy and gene therapy purposes. Adenoviruses from the Atadenovirus genus have been isolated from squamate reptile hosts, ruminants and birds and have a characteristic gene organization and capsid morphology. The carboxy-terminal virus-distal fibre head domains are likely responsible for primary receptor recognition. We determined the high-resolution crystal structure of the Snake Adenovirus 1 (SnAdV-1) fibre head using the multi-wavelength anomalous dispersion (MAD) method. Despite the absence of significant sequence homology, this Atadenovirus fibre head has the same beta-sandwich propeller topology as other adenovirus fibre heads. However, it is about half the size, mainly due to much shorter loops connecting the beta-strands. The detailed structure of the SnAdV-1 fibre head and other animal adenovirus fibre heads, together with the future identification of their natural receptors, may lead to the development of new strategies to target adenovirus vectors to cells of interest.

摘要

腺病毒是无包膜的二十面体病毒,其三聚体纤维蛋白从顶点突出。已知有五个属,其中只有哺乳动物腺病毒属得到了广泛研究。除了将腺病毒作为生物模型系统进行研究以及为预防或对抗病毒感染外,人们对将腺病毒用于疫苗接种、癌症治疗和基因治疗目的也有着浓厚兴趣。来自禽腺病毒属的腺病毒已从有鳞爬行动物宿主、反刍动物和鸟类中分离出来,具有独特的基因组织和衣壳形态。羧基末端病毒远端纤维头部结构域可能负责初级受体识别。我们使用多波长反常色散(MAD)方法确定了蛇腺病毒1(SnAdV-1)纤维头部的高分辨率晶体结构。尽管缺乏显著的序列同源性,但这种禽腺病毒纤维头部与其他腺病毒纤维头部具有相同的β-三明治螺旋桨拓扑结构。然而,它的大小约为其他腺病毒纤维头部的一半,主要原因是连接β-链的环要短得多。SnAdV-1纤维头部和其他动物腺病毒纤维头部的详细结构,以及未来对其天然受体的鉴定,可能会导致开发新的策略,将腺病毒载体靶向到感兴趣的细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4eb/4259310/64a9970b1b2e/pone.0114373.g001.jpg

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