Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein
The flavivirus envelope protein is the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host. We have determined the solution structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JE...
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Veröffentlicht in: | The Journal of biological chemistry 2003-11, Vol.278 (46), p.46007-46013 |
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container_issue | 46 |
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container_title | The Journal of biological chemistry |
container_volume | 278 |
creator | Wu, Kuen-Phon Wu, Chih-Wei Tsao, Ya-Ping Kuo, Ting-Wei Lou, Yuan-Chao Lin, Cheng-Wen Wu, Suh-Chin Cheng, Jya-Wei |
description | The flavivirus envelope protein is the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host. We have determined the solution structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JEV) envelope protein. The JEV domain III forms a beta-barrel type structure composed of six antiparallel beta-strands resembling the immunoglobulin constant domain. We have also identified epitopes of the JEV domain III to its neutralizing antibody by chemical shift perturbation measurements. Site-directed mutagenesis experiments are performed to confirm the NMR results. Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines effective against flaviviruses. |
doi_str_mv | 10.1074/jbc.M307776200 |
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We have determined the solution structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JEV) envelope protein. The JEV domain III forms a beta-barrel type structure composed of six antiparallel beta-strands resembling the immunoglobulin constant domain. We have also identified epitopes of the JEV domain III to its neutralizing antibody by chemical shift perturbation measurements. Site-directed mutagenesis experiments are performed to confirm the NMR results. Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines effective against flaviviruses.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M307776200</identifier><identifier>PMID: 12952958</identifier><language>eng</language><publisher>United States</publisher><subject>Amino Acid Sequence ; Antibodies - chemistry ; Antibodies, Monoclonal ; Antigens - chemistry ; Encephalitis Virus, Japanese - metabolism ; Epitopes ; Flavivirus ; Flavivirus - chemistry ; Flavivirus - metabolism ; Gene Products, env - chemistry ; Gene Products, env - metabolism ; Japanese encephalitis virus ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid</subject><ispartof>The Journal of biological chemistry, 2003-11, Vol.278 (46), p.46007-46013</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12952958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Kuen-Phon</creatorcontrib><creatorcontrib>Wu, Chih-Wei</creatorcontrib><creatorcontrib>Tsao, Ya-Ping</creatorcontrib><creatorcontrib>Kuo, Ting-Wei</creatorcontrib><creatorcontrib>Lou, Yuan-Chao</creatorcontrib><creatorcontrib>Lin, Cheng-Wen</creatorcontrib><creatorcontrib>Wu, Suh-Chin</creatorcontrib><creatorcontrib>Cheng, Jya-Wei</creatorcontrib><title>Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The flavivirus envelope protein is the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host. We have determined the solution structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JEV) envelope protein. The JEV domain III forms a beta-barrel type structure composed of six antiparallel beta-strands resembling the immunoglobulin constant domain. We have also identified epitopes of the JEV domain III to its neutralizing antibody by chemical shift perturbation measurements. Site-directed mutagenesis experiments are performed to confirm the NMR results. Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines effective against flaviviruses.</description><subject>Amino Acid Sequence</subject><subject>Antibodies - chemistry</subject><subject>Antibodies, Monoclonal</subject><subject>Antigens - chemistry</subject><subject>Encephalitis Virus, Japanese - metabolism</subject><subject>Epitopes</subject><subject>Flavivirus</subject><subject>Flavivirus - chemistry</subject><subject>Flavivirus - metabolism</subject><subject>Gene Products, env - chemistry</subject><subject>Gene Products, env - metabolism</subject><subject>Japanese encephalitis virus</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Protein Conformation</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Sequence Homology, Amino Acid</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1LAzEQhoMotlavHiUnb1vz0TS73qT4Ual4UMFbycdsm7JN1k220P4cf6krbYeBgeHleYZB6JqSISVydLfSZvjGiZRyzAg5QX1Kcp5xQb9PUZ8QRrOCibyHLmJcka5GBT1HPcoK0XXeR78fqWlNahtVYa2iiziUWOGyUhu3cU0bcQMmLLzbgcV6i12K2EOburzbOb_Ayieng93e4xiqNrngcTwg4Z-VloBtWCvn8XQ6PW5eVa08RMDgDdTLDpY69V4IfgNVqAHXTUjg_CU6K1UV4eowB-jr6fFz8pLN3p-nk4dZVjOep4yOpbUqt1wKpYVkxIxZwbhkwEooJaG5IERLZpTiRheaCzsGIyQYK5mUgg_Q7Z7beX9aiGm-dtFAVXWXhjbOaUGFyPmoC94cgq1eg53XjVurZjs_fpX_Adkafik</recordid><startdate>20031114</startdate><enddate>20031114</enddate><creator>Wu, Kuen-Phon</creator><creator>Wu, Chih-Wei</creator><creator>Tsao, Ya-Ping</creator><creator>Kuo, Ting-Wei</creator><creator>Lou, Yuan-Chao</creator><creator>Lin, Cheng-Wen</creator><creator>Wu, Suh-Chin</creator><creator>Cheng, Jya-Wei</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20031114</creationdate><title>Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein</title><author>Wu, Kuen-Phon ; Wu, Chih-Wei ; Tsao, Ya-Ping ; Kuo, Ting-Wei ; Lou, Yuan-Chao ; Lin, Cheng-Wen ; Wu, Suh-Chin ; Cheng, Jya-Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p238t-167dda8d375ab5720c6292372e2fef7018500b72caa3cb9b35d6ec57ecd727753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amino Acid Sequence</topic><topic>Antibodies - chemistry</topic><topic>Antibodies, Monoclonal</topic><topic>Antigens - chemistry</topic><topic>Encephalitis Virus, Japanese - metabolism</topic><topic>Epitopes</topic><topic>Flavivirus</topic><topic>Flavivirus - chemistry</topic><topic>Flavivirus - metabolism</topic><topic>Gene Products, env - chemistry</topic><topic>Gene Products, env - metabolism</topic><topic>Japanese encephalitis virus</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Protein Conformation</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Sequence Homology, Amino Acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Kuen-Phon</creatorcontrib><creatorcontrib>Wu, Chih-Wei</creatorcontrib><creatorcontrib>Tsao, Ya-Ping</creatorcontrib><creatorcontrib>Kuo, Ting-Wei</creatorcontrib><creatorcontrib>Lou, Yuan-Chao</creatorcontrib><creatorcontrib>Lin, Cheng-Wen</creatorcontrib><creatorcontrib>Wu, Suh-Chin</creatorcontrib><creatorcontrib>Cheng, Jya-Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Kuen-Phon</au><au>Wu, Chih-Wei</au><au>Tsao, Ya-Ping</au><au>Kuo, Ting-Wei</au><au>Lou, Yuan-Chao</au><au>Lin, Cheng-Wen</au><au>Wu, Suh-Chin</au><au>Cheng, Jya-Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2003-11-14</date><risdate>2003</risdate><volume>278</volume><issue>46</issue><spage>46007</spage><epage>46013</epage><pages>46007-46013</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The flavivirus envelope protein is the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host. We have determined the solution structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JEV) envelope protein. The JEV domain III forms a beta-barrel type structure composed of six antiparallel beta-strands resembling the immunoglobulin constant domain. We have also identified epitopes of the JEV domain III to its neutralizing antibody by chemical shift perturbation measurements. Site-directed mutagenesis experiments are performed to confirm the NMR results. Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines effective against flaviviruses.</abstract><cop>United States</cop><pmid>12952958</pmid><doi>10.1074/jbc.M307776200</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Antibodies - chemistry Antibodies, Monoclonal Antigens - chemistry Encephalitis Virus, Japanese - metabolism Epitopes Flavivirus Flavivirus - chemistry Flavivirus - metabolism Gene Products, env - chemistry Gene Products, env - metabolism Japanese encephalitis virus Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Protein Conformation Protein Structure, Secondary Protein Structure, Tertiary Sequence Homology, Amino Acid |
title | Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein |
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