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构象应激揭示乙肝病毒衣壳的高可塑性

High plasticity of the hepatitis B virus capsid revealed by conformational stress.

作者信息

Böttcher Bettina, Vogel Maren, Ploss Martin, Nassal Michael

机构信息

European Molecular Biology Laboratory, Meyerhofstr. 1, D-69117 Heidelberg, and University Hospital Freiburg Internal Medicine II/Molecular Biology, Germany.

出版信息

J Mol Biol. 2006 Feb 24;356(3):812-22. doi: 10.1016/j.jmb.2005.11.053. Epub 2005 Dec 5.

Abstract

Hepatitis B virus (HBV) replicates through reverse transcription inside its icosahedral nucleocapsid. The internal genome status is signaled to the capsid surface, predicting regulated conformational changes in the capsid structure. To probe their nature and extent, we imposed local conformational stress on the outer surface of HBV capsid-like particles, and monitored its consequences by electron cryomicroscopy and image reconstruction. The capsid structure had an enormous flexibility and robustness as a whole, as well as within the subunits, whose spikes were able to rotate by as much as 40 degrees against the distal interdimer contact sites. The likely hinge for the swiveling movement was the conserved Gly111 residue at the inner surface of the capsid. The stress imposed from the outside also affected the internal capsid organization, implying a specific route for the flow of conformational information between capsid interior and exterior as required for signaling of the genome status.

摘要

乙型肝炎病毒(HBV)通过在其二十面体核衣壳内的逆转录进行复制。内部基因组状态会传递到衣壳表面,预示着衣壳结构会发生有调控的构象变化。为了探究这些变化的性质和程度,我们对HBV衣壳样颗粒的外表面施加局部构象应力,并通过冷冻电子显微镜和图像重建来监测其结果。衣壳结构整体以及亚基内部都具有极大的灵活性和稳健性,其突起能够相对于远端二聚体间接触位点旋转多达40度。旋转运动可能的铰链是衣壳内表面保守的甘氨酸111残基。从外部施加的应力也影响了内部衣壳组织,这意味着在基因组状态信号传导所需的衣壳内部和外部之间存在特定的构象信息流途径。

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