The domains required to direct core proteins of hepatitis C virus and GB virus-B to lipid droplets share common features with plant oleosin proteins
The domains required to direct core proteins of hepatitis C virus and GB virus-B to lipid droplets share common features with plant oleosin proteins
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DOI：
10.1074/jbc.m108798200
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发表时间：
2002-02-08
影响因子：
4.8
通讯作者：
McLauchlan, J
中科院分区：
文献类型：
--
作者：
Hope, RG;Murphy, DJ;McLauchlan, J
在哺乳动物组织培养细胞中，丙型肝炎病毒（HCV）的核心蛋白位于脂滴表面，脂滴是储存脂质的细胞质结构。这种定位所需的关键氨基酸序列位于与 HCV 相关的黄病毒和瘟病毒中不存在的核心蛋白区域。从我们的序列比较来看，HCV核心中的这个区域存在于GBV-B的相应蛋白质中，GBV-B是另一种病毒，其基因组序列与HCV具有显着相似性。假定的 GBV-B 核心蛋白的表达表明它也针对脂滴。通过将比较扩展到细胞蛋白，HCV 核心和植物油质蛋白中脂滴关联的结构域之间存在氨基酸序列相似性。为了确定这些相似性是否在功能上相关，由甘蓝型油菜编码的油质蛋白在不同的哺乳动物细胞系中表达，它保留了与脂滴结合的能力。对缺失突变体的分析表明，对于植物和哺乳动物细胞来说，这种定位所需的蛋白质内的关键区域是相同的。病毒和植物序列的一个共同特征是含有脯氨酸残基的基序。 HCV核心和植物油质蛋白中的这些残基的诱变消除了脂滴关联。最后，HCV核心内与脂滴结合所需的结构域可以替代油质蛋白中的等效结构域，进一步表明病毒和植物序列之间的功能相关性。这些研究发现共同点！脂滴定位所需的不同蛋白质的特征。
In mammalian tissue culture cells, the core protein of hepatitis C virus (HCV) is located at the surface of lipid droplets, which are cytoplasmic structures that store lipid. The critical amino acid sequences necessary for this localization are in a region of core protein that is absent in flavi- and pestiviruses, which are related to HCV. From our sequence comparisons, this region in HCV core was present in the corresponding protein of GBV-B, another virus whose genomic sequence has significant similarity to HCV. Expression of the putative GBV-B core protein revealed that it also was directed to lipid droplets. By extending the comparisons to cellular proteins, there were amino acid sequence similarities between the domains for lipid droplet association in HCV core and plant oleosin proteins. To determine whether these similarities were related functionally, an oleosin encoded by the Brassica napus bniii grene was expressed in different mammalian cell lines, where it retained the capacity to bind to lipid droplets. Analysis of deletion mutants indicated that them critical region within the protein required for this localization was the same for both plant and mammalian cells. A common feature in the viral and plant sequences was a motif containing proline residues. Mutagenesis of these, residues in HCV core and plant oleosin abolished lipid droplet association. Finally, the domain within HCV core required for binding to lipid droplets could substitute for the equivalent domain in oleosin, further indicating the functional relatedness between the viral and plant sequences. These studies identify common! features in disparate proteins that are required for lipid droplet localization.