Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site
Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site
复制标题
通过假定受体结合部位与乙型肝炎病毒相互作用的肽的鉴定和特征描述
DOI：
10.1128/jvi.01270-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Xie, You-hua
中科院分区：
文献类型：
--
作者：
Deng, Qiang;Zhai, Jian-wei;Xie, You-hua
B肝炎病毒（HBV）大包膜蛋白的PreS结构域（特别是氨基酸残基21至47）直接参与病毒与肝细胞的附着，这已由许多先前的研究提出。已经鉴定了几种PreS相互作用蛋白。然而，它们几乎没有共同的序列基序，真正的HBV细胞受体仍然难以捉摸。在这项研究中，我们的目的是确定前S相互作用的基序，并寻找新的HBV相互作用蛋白和长期寻找的受体。以PreS融合蛋白为诱饵筛选噬菌体随机肽库。获得了一组前S结合肽。这些肽可以与PreS 1的氨基酸21至47结合，并且共享足以与PreS和病毒颗粒特异性结合的线性基序（W1T2X3W4W5）。通过BLAST搜索鉴定了几种具有这样的基序的人类蛋白质。对它们的生化和结构特性的分析表明，脂蛋白脂酶（LPL）是脂蛋白代谢的关键酶，可能与PreS和HBV颗粒相互作用。HBV与LPL的相互作用通过体外结合、病毒捕获和细胞附着试验证明。这些结果表明，LPL可能在HBV感染的启动中起作用。识别与HBV包膜结合的LPL对应的肽和蛋白配体将提供抗HBV感染的新的治疗策略。
A direct involvement of the PreS domain of the hepatitis B virus (HBV) large envelope protein, and in particular amino acid residues 21 to 47, in virus attachment to hepatocytes has been suggested by many previous studies. Several PreS-interacting proteins have been identified. However, they share few common sequence motifs, and a bona fide cellular receptor for HBV remains elusive. In this study, we aimed to identify PreS-interacting motifs and to search for novel HBV-interacting proteins and the long-sought receptor. PreS fusion proteins were used as baits to screen a phage display library of random peptides. A group of PreS-binding peptides were obtained. These peptides could bind to amino acids 21 to 47 of PreS1 and shared a linear motif (W1T2X3W4W5) sufficient for binding specifically to PreS and viral particles. Several human proteins with such a motif were identified through BLAST search. Analysis of their biochemical and structural properties suggested that lipoprotein lipase (LPL), a key enzyme in lipoprotein metabolism, might interact with PreS and HBV particles. The interaction of HBV with LPL was demonstrated by in vitro binding, virus capture, and cell attachment assays. These findings suggest that LPL may play a role in the initiation of HBV infection. Identification of peptides and protein ligands corresponding to LPL that bind to the HBV envelope will offer new therapeutic strategies against HBV infection.