Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

Guu, Tom S.Y.; Liu, Zheng; Ye, Qiaozhen; Mata, Douglas A; Li, Kunpeng; Yin, Changcheng; Zhang, Jingqiang; Tao, Yizhi Jane

doi:10.1073/pnas.0904848106

Title: Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

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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-{angstrom} 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:: Guu, Tom S.Y.; Liu, Zheng; Ye, Qiaozhen; Mata, Douglas A; Li, Kunpeng; Yin, Changcheng; Zhang, Jingqiang; Tao, Yizhi Jane

Publication Date:: Tue Aug 25 00:00:00 EDT 2009

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1005756

Resource Type:: Journal Article

Journal Name:: Proc. Natl. Acad. Sci. USA

Additional Journal Information:: Journal Volume: 106; Journal Issue: (31) ; 08, 2009; Journal ID: ISSN 0027-8424

Country of Publication:: United States

Language:: ENGLISH

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; DEVELOPING COUNTRIES; DIMERS; HEPATITIS; MOLECULAR BIOLOGY; PROTEINS; RNA; SACCHAROSE; SIMULATION; VACCINES; VIRUSES

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                    Guu, Tom S.Y., Liu, Zheng, Ye, Qiaozhen, Mata, Douglas A, Li, Kunpeng, Yin, Changcheng, Zhang, Jingqiang, Tao, Yizhi Jane, Sun Yat-Sen), Rice), and Peking). Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding.  United States: N. p., 2009. 
        Web.  doi:10.1073/pnas.0904848106.

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                    Guu, Tom S.Y., Liu, Zheng, Ye, Qiaozhen, Mata, Douglas A, Li, Kunpeng, Yin, Changcheng, Zhang, Jingqiang, Tao, Yizhi Jane, Sun Yat-Sen), Rice), & Peking). Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding.  United States.  https://doi.org/10.1073/pnas.0904848106

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                    Guu, Tom S.Y., Liu, Zheng, Ye, Qiaozhen, Mata, Douglas A, Li, Kunpeng, Yin, Changcheng, Zhang, Jingqiang, Tao, Yizhi Jane, Sun Yat-Sen), Rice), and Peking). 2009.  
        "Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding".  United States.  https://doi.org/10.1073/pnas.0904848106.

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@article{osti_1005756,

  title        = {Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding},

  author       = {Guu, Tom S.Y. and Liu, Zheng and Ye, Qiaozhen and Mata, Douglas A and Li, Kunpeng and Yin, Changcheng and Zhang, Jingqiang and Tao, Yizhi Jane and Sun Yat-Sen) and Rice) and Peking)},

  abstractNote = {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-{angstrom} 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.},

  doi          = {10.1073/pnas.0904848106},

  url          = {https://www.osti.gov/biblio/1005756},
  journal      = {Proc. Natl. Acad. Sci. USA},

  issn         = {0027-8424},

  number       = (31) ; 08, 2009,

  volume       = 106,

  place        = {United States},

  year         = {Tue Aug 25 00:00:00 EDT 2009},

  month        = {Tue Aug 25 00:00:00 EDT 2009}

}

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