Dimerization of Hepatitis E Virus Capsid Protein E2s Domain Is Essential for Virus–Host Interaction

Li, Shaowei; Tang, Xuhua; Seetharaman, J.; Yang, Chunyan; Gu, Ying; Zhang, Jun; Du, Hailian; Shih, J. Wai Kuo; Hew, Choy-Leong; Sivaraman, J.; Xia, Ningshao

doi:10.1371/journal.ppat.1000537

Title: Dimerization of Hepatitis E Virus Capsid Protein E2s Domain Is Essential for Virus–Host Interaction

Journal Article · Fri Aug 07 00:00:00 EDT 2009 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1000537· OSTI ID:1627893

Li, Shaowei ^[1]; Tang, Xuhua ^[2]; Seetharaman, J. ^[3]; Yang, Chunyan ^[1]; Gu, Ying ^[1]; Zhang, Jun ^[1]; Du, Hailian ^[1]; Shih, J. Wai Kuo ^[1]; Hew, Choy-Leong ^[1]; Sivaraman, J. ^[2]; Xia, Ningshao ^[1]

Xiamen University (China)
Xiamen University (China); National University of Singapore (Singapore)
Brookhaven National Laboratory (BNL), Upton, NY (United States)

Hepatitis E virus (HEV), a non-enveloped, positive-stranded RNA virus, is transmitted in a faecal-oral manner, and causes acute liver diseases in humans. The HEV capsid is made up of capsomeres consisting of homodimers of a single structural capsid protein forming the virus shell. These dimers are believed to protrude from the viral surface and to interact with host cells to initiate infection. To date, no structural information is available for any of the HEV proteins. Here, we report for the first time the crystal structure of the HEV capsid protein domain E2s, a protruding domain, together with functional studies to illustrate that this domain forms a tight homodimer and that this dimerization is essential for HEV–host interactions. In addition, we also show that the neutralizing antibody recognition site of HEV is located on the E2s domain. Our study will aid in the development of vaccines and, subsequently, specific inhibitors for HEV.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); Ministry of Education; National Natural Science Foundation; Key Program in Infectious Diseases; People's Republic of China; Academic Research Fund; National University of Singapore

Grant/Contract Number:: SC0012704; B06016; 30500092; 30600106; 30870514; 2006AA020905; 2006AA02A209; 2008ZX10004-015; R154000254112

OSTI ID:: 1627893

Journal Information:: PLoS Pathogens, Vol. 5, Issue 8; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (35)

Automated protein model building combined with iterative structure refinement Perrakis, Anastassis; Morris, Richard; Lamzin, Victor S. Nature Structural Biology, Vol. 6, Issue 5, p. 458-463 https://doi.org/10.1038/8263	journal	May 1999
The Birnavirus Crystal Structure Reveals Structural Relationships among Icosahedral Viruses Coulibaly, Fasséli; Chevalier, Christophe; Gutsche, Irina Cell, Vol. 120, Issue 6 https://doi.org/10.1016/j.cell.2005.01.009	journal	March 2005
Viral Hepatitis during Pregnancy Kehayoglou, Kyriakos A.; Stavropoulos, Aristotelis K.; Lolis, Dimitrios E. International Journal of Gynecology & Obstetrics, Vol. 10, Issue 3 https://doi.org/10.1002/j.1879-3479.1972.tb00830.x	journal	May 1972
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination Brünger, A. T.; Adams, P. D.; Clore, G. M. Acta Crystallographica Section D Biological Crystallography, Vol. 54, Issue 5 https://doi.org/10.1107/S0907444998003254	journal	September 1998
Raster3D Version 2.0. A program for photorealistic molecular graphics Merritt, E. A.; Murphy, M. E. P. Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 6 https://doi.org/10.1107/S0907444994006396	journal	November 1994
Viral Hepatitis During Pregnancy Adams, Reuben H. JAMA: The Journal of the American Medical Association, Vol. 192, Issue 3 https://doi.org/10.1001/jama.1965.03080160015003	journal	April 1965
PROCHECK: a program to check the stereochemical quality of protein structures Laskowski, R. A.; MacArthur, M. W.; Moss, D. S. Journal of Applied Crystallography, Vol. 26, Issue 2 https://doi.org/10.1107/S0021889892009944	journal	April 1993
Hepatitis E: An emerging awareness of an old disease Purcell, R. H.; Emerson, S. U. Journal of Hepatology, Vol. 48, Issue 3 https://doi.org/10.1016/j.jhep.2007.12.008	journal	March 2008
X-ray Crystallographic Structure of the Norwalk Virus Capsid Prasad, B. V. V. Science, Vol. 286, Issue 5438 https://doi.org/10.1126/science.286.5438.287	journal	October 1999
Conformational exchange in the potassium channel blocker ShK Iwakawa, Naoto; Baxter, Nicola J.; Wai, Dorothy C. C. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-55806-3	journal	December 2019
A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates Li, Shao W.; Zhang, Jun; Li, Yi M. Vaccine, Vol. 23, Issue 22 https://doi.org/10.1016/j.vaccine.2004.11.064	journal	April 2005
Analysis of hepatitis E virus neutralization sites using monoclonal antibodies directed against a virus capsid protein Zhang, Jun; Gu, Ying; Ge, Sheng X. Vaccine, Vol. 23, Issue 22 https://doi.org/10.1016/j.vaccine.2004.11.065	journal	April 2005
Putative receptor-binding sites of hepatitis E virus He, Shuizhen; Miao, Ji; Zheng, Zizheng Journal of General Virology, Vol. 89, Issue 1 https://doi.org/10.1099/vir.0.83308-0	journal	January 2008
Improved methods for building protein models in electron density maps and the location of errors in these models Jones, T. A.; Zou, J. Y.; Cowan, S. W. Acta Crystallographica Section A Foundations of Crystallography, Vol. 47, Issue 2, p. 110-119 https://doi.org/10.1107/S0108767390010224	journal	March 1991
Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling Schuck, Peter Biophysical Journal, Vol. 78, Issue 3 https://doi.org/10.1016/S0006-3495(00)76713-0	journal	March 2000
Icosahedral RNA Virus Structure Rossmann, M. G.; Johnson, J. E. Annual Review of Biochemistry, Vol. 58, Issue 1 https://doi.org/10.1146/annurev.bi.58.070189.002533	journal	June 1989
Mutations within the P2 Domain of Norovirus Capsid Affect Binding to Human Histo-Blood Group Antigens: Evidence for a Binding Pocket Tan, Ming; Huang, Pengwei; Meller, Jaroslaw Journal of Virology, Vol. 77, Issue 23 https://doi.org/10.1128/JVI.77.23.12562-12571.2003	journal	December 2003
Touring protein fold space with Dali/FSSP Holm, L. Nucleic Acids Research, Vol. 26, Issue 1 https://doi.org/10.1093/nar/26.1.316	journal	January 1998
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
The design and implementation of SnB version 2.0 Weeks, Charles M.; Miller, Russ Journal of Applied Crystallography, Vol. 32, Issue 1 https://doi.org/10.1107/S0021889898010504	journal	February 1999
Analysis of data from the analytical ultracentrifuge by nonlinear least-squares techniques Johnson, M. L.; Correia, J. J.; Yphantis, D. A. Biophysical Journal, Vol. 36, Issue 3 https://doi.org/10.1016/S0006-3495(81)84753-4	journal	December 1981
Mutations within the P2 Domain of Norovirus Capsid Affect Binding to Human Histo-Blood Group Antigens: Evidence for a Binding Pocket Tan, Ming; Huang, Pengwei; Meller, Jaroslaw Journal of Virology, Vol. 78, Issue 6 https://doi.org/10.1128/jvi.78.6.3201.2004	journal	March 2004
Viral Hepatitis During Pregnancy Borhanmanesh, Fathali; Haghighi, Parviz; Hekmat, Keyoumars Obstetrical & Gynecological Survey, Vol. 28, Issue 9 https://doi.org/10.1097/00006254-197309000-00005	journal	January 1973
X-ray structure of a native calicivirus: Structural insights into antigenic diversity and host specificity Chen, R.; Neill, J. D.; Estes, M. K. Proceedings of the National Academy of Sciences, Vol. 103, Issue 21 https://doi.org/10.1073/pnas.0600421103	journal	May 2006
Virus Taxonomy – 1999: The Universal System of Virus Taxonomy, updated to include the new proposals ratified by the International Committee on Taxonomy of Viruses during 1998 Pringle, C. R. Archives of Virology, Vol. 144, Issue 2 https://doi.org/10.1007/s007050050515	journal	February 1999
Conformational antigenic determinants generated by interactions between a bacterially expressed recombinant peptide of the hepatitis E virus structural protein Zhang, Ji-Zhong; Ng, Mun H.; Xia, N. S. Journal of Medical Virology, Vol. 64, Issue 2 https://doi.org/10.1002/jmv.1027	journal	January 2001
Evolutionary Trace Residues in Noroviruses: Importance in Receptor Binding, Antigenicity, Virion Assembly, and Strain Diversity Chakravarty, Sugoto; Hutson, Anne M.; Estes, Mary K. Journal of Virology, Vol. 79, Issue 1 https://doi.org/10.1128/JVI.79.1.554-568.2005	journal	January 2005
Recombinant Hepatitis E Capsid Protein Self-Assembles into a Dual-Domain T = 1 Particle Presenting Native Virus Epitopes Xing, Li; Kato, Kenzo; Li, Tiancheng Virology, Vol. 265, Issue 1 https://doi.org/10.1006/viro.1999.0005	journal	December 1999
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
SOLVE and RESOLVE: automated structure solution, density modification and model building Terwilliger, Thomas Journal of Synchrotron Radiation, Vol. 11, Issue 1 https://doi.org/10.1107/S0909049503023938	journal	November 2003
A factor preventing the major head protein of bacteriophage T4 from random aggregation Laemmli, U. K.; Beguin, F.; Gujer-Kellenberger, G. Journal of Molecular Biology, Vol. 47, Issue 1 https://doi.org/10.1016/0022-2836(70)90402-x	journal	January 1970
Viral hepatitis during pregnancy Jaiswal, S. P. B.; Jain, A. K.; Naik, G. International Journal of Gynecology & Obstetrics, Vol. 72, Issue 2 https://doi.org/10.1016/s0020-7292(00)00264-2	journal	February 2001
Hepatitis E: an overview Worm, Harald C.; van der Poel, Wim H. M.; Brandstätter, Gerald Microbes and Infection, Vol. 4, Issue 6 https://doi.org/10.1016/s1286-4579(02)01584-8	journal	May 2002
Mutational Analysis of Essential Interactions Involved in the Assembly of Hepatitis E Virus Capsid Li, Shao-Wei; Zhang, Jun; He, Zhi-Qiang Journal of Biological Chemistry, Vol. 280, Issue 5 https://doi.org/10.1074/jbc.m410361200	journal	February 2005
The P Domain of Norovirus Capsid Protein Forms Dimer and Binds to Histo-Blood Group Antigen Receptors Tan, Ming; Hegde, Rashmi S.; Jiang, Xi Journal of Virology, Vol. 78, Issue 12 https://doi.org/10.1128/jvi.78.12.6233-6242.2004	journal	June 2004

Cited By (28)

Characterization of Three Novel Linear Neutralizing B-Cell Epitopes in the Capsid Protein of Swine Hepatitis E Virus Chen, Yiyang; Liu, Baoyuan; Sun, Yani Journal of Virology, Vol. 92, Issue 13 https://doi.org/10.1128/jvi.00251-18	journal	July 2018
Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins Zhang, Xiao; Xin, Lu; Li, Shaowei Human Vaccines & Immunotherapeutics, Vol. 11, Issue 5 https://doi.org/10.1080/21645515.2015.1016675	journal	March 2015
A Comprehensive Study of Neutralizing Antigenic Sites on the Hepatitis E Virus (HEV) Capsid by Constructing, Clustering, and Characterizing a Tool Box Zhao, Min; Li, Xiao-Jing; Tang, Zi-Min Journal of Biological Chemistry, Vol. 290, Issue 32 https://doi.org/10.1074/jbc.m115.649764	journal	August 2015
Functional epitopes on hepatitis E virions and recombinant capsids are highly conformation-dependent He, Bin; Zhang, Zhigang; Zhang, Xinyuan Human Vaccines & Immunotherapeutics, Vol. 16, Issue 7 https://doi.org/10.1080/21645515.2019.1703454	journal	January 2020
Generation in yeast and antigenic characterization of hepatitis E virus capsid protein virus-like particles Simanavicius, Martynas; Tamosiunas, Paulius Lukas; Petraityte-Burneikiene, Rasa Applied Microbiology and Biotechnology, Vol. 102, Issue 1 https://doi.org/10.1007/s00253-017-8622-9	journal	November 2017
Effects of mRNA secondary structure on the expression of HEV ORF2 proteins in Escherichia coli Behloul, Nouredine; Wei, Wenjuan; Baha, Sarra Microbial Cell Factories, Vol. 16, Issue 1 https://doi.org/10.1186/s12934-017-0812-8	journal	November 2017
Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody Gu, Ying; Tang, Xuhua; Zhang, Xiao Cell Research, Vol. 25, Issue 5 https://doi.org/10.1038/cr.2015.34	journal	March 2015
Hepatitis E vaccine development: A 14 year odyssey Wu, Ting; Li, Shao-Wei; Zhang, Jun Human Vaccines & Immunotherapeutics, Vol. 8, Issue 6 https://doi.org/10.4161/hv.20042	journal	June 2012
Immunization against Hepatitis E Innis, Bruce L.; Lynch, Julia A. Cold Spring Harbor Perspectives in Medicine, Vol. 8, Issue 11 https://doi.org/10.1101/cshperspect.a032573	journal	March 2018
Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection Yin, Xin; Ying, Dong; Lhomme, Sébastien Proceedings of the National Academy of Sciences, Vol. 115, Issue 18 https://doi.org/10.1073/pnas.1721345115	journal	April 2018
Profile of Acute Infectious Markers in Sporadic Hepatitis E Huang, Shoujie; Zhang, Xuefeng; Jiang, Hanmin PLoS ONE, Vol. 5, Issue 10 https://doi.org/10.1371/journal.pone.0013560	journal	October 2010
Design and development of a chimeric vaccine candidate against zoonotic hepatitis E and foot-and-mouth disease Behloul, Nouredine; Baha, Sarra; Liu, Zhenzhen Microbial Cell Factories, Vol. 19, Issue 1 https://doi.org/10.1186/s12934-020-01394-1	journal	July 2020
Hepatitis E Virus Assembly and Release Ju, Xiaohui; Ding, Qiang Viruses, Vol. 11, Issue 6 https://doi.org/10.3390/v11060539	journal	June 2019
The atomic structures of shrimp nodaviruses reveal new dimeric spike structures and particle polymorphism Chen, Nai-Chi; Yoshimura, Masato; Miyazaki, Naoyuki Communications Biology, Vol. 2, Issue 1 https://doi.org/10.1038/s42003-019-0311-z	journal	February 2019
Structural basis for the neutralization and genotype specificity of hepatitis E virus Tang, X.; Yang, C.; Gu, Y. Proceedings of the National Academy of Sciences, Vol. 108, Issue 25 https://doi.org/10.1073/pnas.1101309108	journal	June 2011
Viral neutralization by antibody-imposed physical disruption Zheng, Qingbing; Jiang, Jie; He, Maozhou Proceedings of the National Academy of Sciences, Vol. 116, Issue 52 https://doi.org/10.1073/pnas.1916028116	journal	December 2019
Molecular biology and replication of hepatitis E virus Cao, Dianjun; Meng, Xiang-Jin Emerging Microbes & Infections, Vol. 1, Issue 1 https://doi.org/10.1038/emi.2012.7	journal	July 2012
Prophylactic Hepatitis E Vaccines: Antigenic Analysis and Serological Evaluation Li, Yike; Huang, Xiaofen; Zhang, Zhigang Viruses, Vol. 12, Issue 1 https://doi.org/10.3390/v12010109	journal	January 2020
Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity and efficacy Zhao, Qinjian; Zhang, Jun; Wu, Ting Journal of Gastroenterology, Vol. 48, Issue 2 https://doi.org/10.1007/s00535-012-0701-1	journal	November 2012
Molecular virology of hepatitis E virus Ahmad, Imran; Holla, R. Prasida; Jameel, Shahid Virus Research, Vol. 161, Issue 1 https://doi.org/10.1016/j.virusres.2011.02.011	journal	October 2011
Author Correction: Dimerization: a structural feature for the protection of hepatitis E virus capsid protein against trypsinization Wei, Wenjuan; Behloul, Nouredine; Baha, Sarra Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-24852-8	journal	April 2018
A high-throughput neutralizing assay for antibodies and sera against hepatitis E virus Cai, Wei; Tang, Zi-Min; Wen, Gui-Ping Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep25141	journal	April 2016
Enhanced humoral response in pregnant mice immunized with liposome encapsulated recombinant neutralizing epitope protein of Hepatitis- E virus Joshi, Shivali Shirish; Arankalle, Vidya Avinash Virology Journal, Vol. 12, Issue 1 https://doi.org/10.1186/s12985-015-0302-8	journal	May 2015
Peptides Interfering 3A Protein Dimerization Decrease FMDV Multiplication González-Magaldi, Mónica; Vázquez-Calvo, Ángela; de la Torre, Beatriz G. PLOS ONE, Vol. 10, Issue 10 https://doi.org/10.1371/journal.pone.0141415	journal	October 2015
C-Terminal Amino Acids 471-507 of Avian Hepatitis E Virus Capsid Protein Are Crucial for Binding to Avian and Human Cells Zhang, Xinquan; Bilic, Ivana; Marek, Ana PLOS ONE, Vol. 11, Issue 4 https://doi.org/10.1371/journal.pone.0153723	journal	April 2016
Transmission, diagnosis, and management of hepatitis E: an update Mirazo, Santiago; Ramos, Natalia; Mainardi, Victoria Hepatic Medicine: Evidence and Research https://doi.org/10.2147/hmer.s63417	journal	June 2014
Hepatitis E Virus Entry Viruses, Vol. 11, Issue 10 https://doi.org/10.3390/v11100883	journal	September 2019
Hepatitis E virus as an emerging zoonotic pathogen Park, Woo-Jung; Park, Byung-Joo; Ahn, Hee-Seop Journal of Veterinary Science, Vol. 17, Issue 1 https://doi.org/10.4142/jvs.2016.17.1.1	journal	January 2016

Similar Records

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

Journal Article · Tue Aug 25 00:00:00 EDT 2009 · Proc. Natl. Acad. Sci. USA · OSTI ID:1627893

Guu, Tom S.Y.; Liu, Zheng; Ye, Qiaozhen; +5 more

Crystal Structure of the Human Astrovirus Capsid Protein

Journal Article · Wed Jul 27 00:00:00 EDT 2016 · Journal of Virology · OSTI ID:1627893

Toh, Yukimatsu; Harper, Justin; Dryden, Kelly A.; +4 more

Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

Journal Article · Tue Aug 26 00:00:00 EDT 2014 · Science · OSTI ID:1627893

Kong, Leopold; Giang, Erick; Nieusma, Travis; +9 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
hepatitis E virus
dimers
dimerization
viral packaging
antibodies
protein domains
crystal structure
point mutation

Title: Dimerization of Hepatitis E Virus Capsid Protein E2s Domain Is Essential for Virus–Host Interaction

Citation Formats

References (35)

Cited By (28)

Similar Records

Related Subjects