title: Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding.
abstract: Hepatitis E virus (HEV), a small, non-enveloped RNA virus in the family Hepeviridae, is associated with endemic and epidemic acute viral hepatitis in developing countries. Our 3.5-A structure of a HEV-like particle (VLP) shows that each capsid protein contains 3 linear domains that form distinct structural elements: S, the continuous capsid; P1, 3-fold protrusions; and P2, 2-fold spikes. The S domain adopts a jelly-roll fold commonly observed in small RNA viruses. The P1 and P2 domains both adopt beta-barrel folds. Each domain possesses a potential polysaccharide-binding site that may function in cell-receptor binding. Sugar binding to P1 at the capsid protein interface may lead to capsid disassembly and cell entry. Structural modeling indicates that native T = 3 capsid contains flat dimers, with less curvature than those of T = 1 VLP. Our findings significantly advance the understanding of HEV molecular biology and have application to the development of vaccines and antiviral medications.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Tom S Y
authors.initials: TS
authors.lastname: Guu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Qiaozhen
authors.initials: Q
authors.lastname: Ye
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Mata
authors.forename: Kunpeng
authors.initials: K
authors.lastname: Li
authors.forename: Changcheng
authors.initials: C
authors.lastname: Yin
authors.forename: Jingqiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Yizhi Jane
authors.initials: YJ
authors.lastname: Tao
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry*; D019281:Dimerization; D016752:Hepatitis E virus / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000502:physiology*; D014771:Virion / Q000737:chemistry*; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; D011134:Polysaccharides; D011991:Receptors, Virus