摘要
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.
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.
基金
ACKNOWLEDGEMENTS We thank Neil Shaw, Haitao Yang, Fei Sun, Yuguang Zhao, Jingshan Ren, David I. Stuart and Elizabeth E. Fry for assistance with the manuscript and advice, Wei Peng, Pi Liu, Jialong Zhang provided expert assistance. We gratefully acknowledge the assistance of the staff of the beamline BL5A and BL17A at the Photon Factory （PF） in Japan with the X-ray diffraction data col- lection. We also thank Core Facility in the Institute of Biophysics, Chinese Academy of Sciences （CAS）. Work was supported by the National Basic Research Program （973 Program） （No. 2014CB542800）, National Natural Science Foundation of China （Grant No. 81330036） and the Strategic Priority Research Program of the Chinese Academy of Sciences, （Grant No. XDB08020200）.
