Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype
Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype
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DOI：
10.1016/j.jmb.2018.10.018
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发表时间：
2018-12-07
影响因子：
5.6
通讯作者：
Nassal, Michael
中科院分区：
文献类型：
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作者：
Boettcher, Bettina;Nassal, Michael
乙肝病毒是一种主要的人类病原体，它由一个被二十面体有序的核心蛋白包围的病毒基因组和一个密集填充表面蛋白的多态、脂类包膜组成。核心蛋白的点突变，即第97位的苯丙氨酸被交换为较小的亮氨酸，会导致衣壳在基因组完全成熟之前过早包膜。我们使用电子冷冻显微镜，RID图像处理来研究在2.6到2.8埃分辨率下点突变是如何影响衣壳结构的。我们发现，在突变体中，第97位的较小侧链发生了移位，增加了衣壳棘突中心相邻口袋的大小。在突变体中，这个口袋里充满了一种未知的密度。突变体未分辨的C-末端结构域中丝氨酸残基的磷酸化使有序衣壳的结构基本保持不变。然而，我们能够分解在磷酸化位点之前的Pro 144下游的几个先前未分解的残基。这些残基堆积在邻近的亚基上，增加了二聚体之间的接触，表明C-末端在衣壳稳定中发挥了重要作用，并提供了比先前观察到的更大的相互作用界面。(C)2018爱思唯尔有限公司。保留所有权利。
Hepatitis B virus is a major human pathogen that consists of a viral genome surrounded by an icosahedrally ordered core protein and a polymorphic, lipidic envelope that is densely packed with surface proteins. A point mutation in the core protein in which a phenylalanine at position 97 is exchanged for a smaller leucine leads to premature envelopment of the capsid before the genome maturation is fully completed. We have used electron cryo-microscopy,rid image processing to investigate how the point mutation affects the structure of the capsid at 2.6- to 2.8 angstrom-resolution. We found that in the mutant the smaller side chain at position 97 is displaced, increasing the size of an adjacent pocket in the center of the spikes of the capsid. In the mutant, this pocket is filled with an unknown density. Phosphorylation of serine residues in the unresolved C-terminal domain of the mutant leaves the structure of the ordered capsid largely unchanged. However, we were able to resolve several previously unresolved residues downstream of proline 144 that precede the phosphorylationsites. These residues pack against the neighboring subunits and increase the inter-dimer contact suggesting that the C-termini play an important role in capsid stabilization and provide a much larger interaction interface than previously observed. (C) 2018 Elsevier Ltd. All rights reserved.