title: Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71.
abstract: 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.
authors.affiliation: National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Dang
authors.forename: Xiangxi
authors.initials: X
authors.lastname: Wang
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Lin
authors.forename: Yuna
authors.initials: Y
authors.lastname: Sun
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000143:Acids / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029821:Enterovirus A, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051907:Lysosomal Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D061987:Sf9 Cells; D055672:Static Electricity; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D000143:Acids; D036022:Capsid Proteins; D051907:Lysosomal Membrane Proteins; D012367:RNA, Viral; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human