Structural determinants that target the hepatitis C virus core protein to lipid droplets
Structural determinants that target the hepatitis C virus core protein to lipid droplets
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DOI：
10.1074/jbc.m601031200
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发表时间：
2006-08-04
影响因子：
4.8
通讯作者：
McLauchlan, John
中科院分区：
文献类型：
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作者：
Boulant, Steeve;Montserret, Roland;McLauchlan, John
丙型肝炎病毒核心蛋白通过其C-末端结构域（称为D2）靶向作为细胞内储存细胞器的脂滴。从圆二色性和核磁共振分析，我们表明，D2内的主要结构元素由两个两亲性α-螺旋（HALPHIA I和HALPHIA II）分离的疏水环。这两种螺旋都需要一个疏水环境来折叠，这表明脂质相互作用有助于它们的结构完整性。突变的研究表明，一个组合的HSP 7I，疏水环，和HSP 7II是必不可少的有效的脂滴协会，并指出在磷脂层界面的两个螺旋的平面膜相互作用。除了脂滴协会，膜相互作用的D2是必要的折叠和稳定的核心成熟后，在内质网膜的信号肽肽酶。这些研究确定了靶向结构域中的关键决定因素，这些决定因素使病毒蛋白能够运输和附着到脂滴上。它们也作为一个独特的模型，用于阐明两个膜结合细胞器之间的蛋白质-脂质相互作用的特异性。
Hepatitis C virus core protein is targeted to lipid droplets, which serve as intracellular storage organelles, by its C-terminal domain, termed D2. From circular dichroism and nuclear magnetic resonance analyses, we demonstrate that the major structural elements within D2 consist of two amphipathic alpha-helices (Helix I and Helix II) separated by a hydrophobic loop. Both helices require a hydrophobic environment for folding, indicating that lipid interactions contribute to their structural integrity. Mutational studies revealed that a combination of Helix I, the hydrophobic loop, and Helix II is essential for efficient lipid droplet association and pointed to an in-plane membrane interaction of the two helices at the phospholipid layer interface. Aside from lipid droplet association, membrane interaction of D2 is necessary for folding and stability of core following maturation at the endoplasmic reticulum membrane by signal peptide peptidase. These studies identify critical determinants within a targeting domain that enable trafficking and attachment of a viral protein to lipid droplets. They also serve as a unique model for elucidating the specificity of protein-lipid interactions between two membrane-bound organelles.