Dang Minghao, Wang Xiangxi, Wang Quan, Wang Yaxin, Lin Jianping, Sun Yuna, Li Xuemei, Zhang Liguo, Lou Zhiyong, Wang Junzhi, Rao Zihe
National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.
Protein Cell. 2014 Sep;5(9):692-703. doi: 10.1007/s13238-014-0087-3. Epub 2014 Jul 2.
Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.
与包膜病毒进入细胞的机制已明确不同，非包膜真核病毒进入细胞的机制在很大程度上仍不清楚。微小核糖核酸病毒是这类病毒的代表性模型，它们通过功能性受体启动这一进入过程。在此，我们展示了对重要人类肠道病毒71型（EV71）的功能性受体SCARB2的结构和功能研究。SCARB2负责EV71的附着以及脱壳。中性和酸性条件下SCARB2结构的差异表明，SCARB2经历了关键的pH依赖性构象变化，该变化打开了一个脂质转移通道，以介导疏水口袋因子从病毒体中排出，这是脱壳的先决条件。我们还确定了与SCARB2附着所必需的关键残基，确定EV71的峡谷区域介导受体相互作用。这些结果共同为肠道病毒的细胞附着和脱壳起始提供了清晰的认识。
