New Structural Insights into the Genome and Minor Capsid Proteins of BK Polyomavirus using Cryo-Electron Microscopy.

New Structural Insights into the Genome and Minor Capsid Proteins of BK Polyomavirus using Cryo-Electron Microscopy.
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DOI:
10.1016/j.str.2016.02.008
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发表时间:
2016-04-05
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Ranson NA
Ranson NA
中科院分区:
其他
文献类型:
--
作者:
Hurdiss DL;Morgan EL;Thompson RF;Prescott EL;Panou MM;Macdonald A;Ranson NA

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BK多瘤病毒是移植患者多种疾病的病原体,其免疫功能受到抑制.为了更好地了解BK的结构和生活周期,我们在细胞培养中产生了感染性病毒粒子和仅VP1病毒样颗粒,并利用冷冻电子显微镜(EM)和单粒子图像处理技术确定了它们的三维结构。由此得到的BK的7.6?分辨率结构和病毒样颗粒的9.1?分辨率是任何多瘤病毒的最高分辨率的冷冻-EM结构。这些结构证实了这些人类多瘤病毒主要结构蛋白成分的结构与其他宿主以前的结构相似,但为神秘的次要结构蛋白VP2和VP3的位置和作用提供了新的见解。我们还观察到两个电子密度壳,我们将其归因于病毒基因组的结构有序部分,以及这种密度与VP1和次要衣壳蛋白之间的离散接触。第一张BK多瘤病毒的3D结构图显示了微小衣壳蛋白的位置和范围,确定了所有三种结构蛋白和包装基因组之间的联系,描述了病毒微小染色体Hurdiss等人的结构组织。以7.6°的分辨率展示了人类BK多瘤病毒的第一个结构,并在类似分辨率下与仅VP1的VLP进行了比较,为微小衣壳蛋白的位置、基因组识别和病毒微染色体的组织提供了新的见解。
BK polyomavirus is the causative agent of several diseases in transplant patients and the immunosuppressed. In order to better understand the structure and life cycle of BK, we produced infectious virions and VP1-only virus-like particles in cell culture, and determined their three-dimensional structures using cryo-electron microscopy (EM) and single-particle image processing. The resulting 7.6-Å resolution structure of BK and 9.1-Å resolution of the virus-like particles are the highest-resolution cryo-EM structures of any polyomavirus. These structures confirm that the architecture of the major structural protein components of these human polyomaviruses are similar to previous structures from other hosts, but give new insight into the location and role of the enigmatic minor structural proteins, VP2 and VP3. We also observe two shells of electron density, which we attribute to a structurally ordered part of the viral genome, and discrete contacts between this density and both VP1 and the minor capsid proteins. The first 3D structure of native, infectious, human BK polyomavirus Show the location and extent of the minor capsid proteins Identify contacts between all three structural proteins and the packaged genome Describe structural organization within the viral minichromosome Hurdiss et al. present the first structure of human BK polyomavirus at 7.6 Å and compare it with a VP1-only VLP at similar resolution, providing new insights into the location of minor capsid proteins, genome recognition, and organization of the viral minichromosome.