Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding.
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.
Guu
Tom S Y
TS
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
Liu
Zheng
Z
Ye
Qiaozhen
Q
Mata
Douglas A
DA
Li
Kunpeng
K
Yin
Changcheng
C
Zhang
Jingqiang
J
Tao
Yizhi Jane
YJ
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
D036022:Capsid Proteins; D011134:Polysaccharides; D011991:Receptors, Virus