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Modeling a Sialic Acid Binding Pocket in the External Loops of JC Virus VP1
JC virus (JCV) is a common human polyomavirus that infects over 70% of the population worldwide. JCV has a restricted cell tropism that is caused partly by the initial interaction between the virus and sialic acid-containing host cell receptors. To identify the molecular interactions between the vir...
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| Published in: | The Journal of biological chemistry 2004-11, Vol.279 (47), p.49172-49176 |
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| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
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| container_end_page | 49176 |
| container_issue | 47 |
| container_start_page | 49172 |
| container_title | The Journal of biological chemistry |
| container_volume | 279 |
| creator | Gee, Gretchen V Tsomaia, Natia Mierke, Dale F Atwood, Walter J |
| description | JC virus (JCV) is a common human polyomavirus that infects over 70% of the population worldwide. JCV has a restricted cell
tropism that is caused partly by the initial interaction between the virus and sialic acid-containing host cell receptors.
To identify the molecular interactions between the virus and its cellular receptor, we used a combined approach of site-directed
mutagenesis and homology-based molecular modeling. A model of the major viral capsid protein VP1 based on sequence alignment
with other closely related polyomaviruses allowed us to target specific amino acids in the extracellular loops of VP1 for
mutagenesis. An analysis of the growth rates of 17 point mutants led to the identification of VP1 amino acids that are critical
in virus-host cell receptor interactions. Molecular dynamics simulations were then used to build and confirm a model of the
interaction between VP1 and the sialic acid component of the JCV receptor. |
| doi_str_mv | 10.1074/jbc.M409326200 |
| format | article |
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tropism that is caused partly by the initial interaction between the virus and sialic acid-containing host cell receptors.
To identify the molecular interactions between the virus and its cellular receptor, we used a combined approach of site-directed
mutagenesis and homology-based molecular modeling. A model of the major viral capsid protein VP1 based on sequence alignment
with other closely related polyomaviruses allowed us to target specific amino acids in the extracellular loops of VP1 for
mutagenesis. An analysis of the growth rates of 17 point mutants led to the identification of VP1 amino acids that are critical
in virus-host cell receptor interactions. Molecular dynamics simulations were then used to build and confirm a model of the
interaction between VP1 and the sialic acid component of the JCV receptor.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M409326200</identifier><identifier>PMID: 15347668</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Binding Sites ; Capsid ; Capsid Proteins - chemistry ; Cell Line ; Cell Nucleus - virology ; Computer Simulation ; Fluorescent Antibody Technique, Indirect ; Humans ; JC virus ; Microscopy, Electron ; Models, Molecular ; Mutagenesis, Site-Directed ; N-Acetylneuraminic Acid - chemistry ; Neuroglia - cytology ; Neuroglia - virology ; Plasmids - metabolism ; Polyomavirus ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Time Factors ; Transfection</subject><ispartof>The Journal of biological chemistry, 2004-11, Vol.279 (47), p.49172-49176</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-ca8ffc6d2ba32cc8627b7cb6d0a7305665bb904ad954fc4836fc00e1dba307333</citedby><cites>FETCH-LOGICAL-c459t-ca8ffc6d2ba32cc8627b7cb6d0a7305665bb904ad954fc4836fc00e1dba307333</cites></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/15347668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gee, Gretchen V</creatorcontrib><creatorcontrib>Tsomaia, Natia</creatorcontrib><creatorcontrib>Mierke, Dale F</creatorcontrib><creatorcontrib>Atwood, Walter J</creatorcontrib><title>Modeling a Sialic Acid Binding Pocket in the External Loops of JC Virus VP1</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>JC virus (JCV) is a common human polyomavirus that infects over 70% of the population worldwide. JCV has a restricted cell
tropism that is caused partly by the initial interaction between the virus and sialic acid-containing host cell receptors.
To identify the molecular interactions between the virus and its cellular receptor, we used a combined approach of site-directed
mutagenesis and homology-based molecular modeling. A model of the major viral capsid protein VP1 based on sequence alignment
with other closely related polyomaviruses allowed us to target specific amino acids in the extracellular loops of VP1 for
mutagenesis. An analysis of the growth rates of 17 point mutants led to the identification of VP1 amino acids that are critical
in virus-host cell receptor interactions. Molecular dynamics simulations were then used to build and confirm a model of the
interaction between VP1 and the sialic acid component of the JCV receptor.</description><subject>Binding Sites</subject><subject>Capsid</subject><subject>Capsid Proteins - chemistry</subject><subject>Cell Line</subject><subject>Cell Nucleus - virology</subject><subject>Computer Simulation</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Humans</subject><subject>JC virus</subject><subject>Microscopy, Electron</subject><subject>Models, Molecular</subject><subject>Mutagenesis, Site-Directed</subject><subject>N-Acetylneuraminic Acid - chemistry</subject><subject>Neuroglia - cytology</subject><subject>Neuroglia - virology</subject><subject>Plasmids - metabolism</subject><subject>Polyomavirus</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Protein Structure, Tertiary</subject><subject>Time Factors</subject><subject>Transfection</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNpFkM1PwjAYxhujEUSvHk0PxtuwX2u3IxL8hEiiEm9N13WsOFZst6j_vSOQ8Fze5MnvfQ4_AC4xGmIk2O0q08MZQyklnCB0BPoYJTSiMf48Bn2ECI5SEic9cBbCCnVhKT4FPRxTJjhP-uBl5nJT2XoJFXyzqrIajrTN4Z2t8207d_rLNNDWsCkNnPw2xteqglPnNgG6Aj6P4cL6NsDFHJ-Dk0JVwVzs7wB83E_ex4_R9PXhaTyaRprFaRNplRSF5jnJFCVaJ5yITOiM50gJimLO4yxLEVN5GrNCs4TyQiNkcN7xSFBKB-Bmt7vx7rs1oZFrG7SpKlUb1waJhUjSmLAOHO5A7V0I3hRy4-1a-T-Jkdzqk50-edDXPVztl9tsbfIDvvfVAdc7oLTL8sd6IzPrdGnWkohUMiE7v4LQf7EldVU</recordid><startdate>20041119</startdate><enddate>20041119</enddate><creator>Gee, Gretchen V</creator><creator>Tsomaia, Natia</creator><creator>Mierke, Dale F</creator><creator>Atwood, Walter J</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20041119</creationdate><title>Modeling a Sialic Acid Binding Pocket in the External Loops of JC Virus VP1</title><author>Gee, Gretchen V ; Tsomaia, Natia ; Mierke, Dale F ; Atwood, Walter J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-ca8ffc6d2ba32cc8627b7cb6d0a7305665bb904ad954fc4836fc00e1dba307333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Binding Sites</topic><topic>Capsid</topic><topic>Capsid Proteins - chemistry</topic><topic>Cell Line</topic><topic>Cell Nucleus - virology</topic><topic>Computer Simulation</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Humans</topic><topic>JC virus</topic><topic>Microscopy, Electron</topic><topic>Models, Molecular</topic><topic>Mutagenesis, Site-Directed</topic><topic>N-Acetylneuraminic Acid - chemistry</topic><topic>Neuroglia - cytology</topic><topic>Neuroglia - virology</topic><topic>Plasmids - metabolism</topic><topic>Polyomavirus</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Protein Structure, Tertiary</topic><topic>Time Factors</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gee, Gretchen V</creatorcontrib><creatorcontrib>Tsomaia, Natia</creatorcontrib><creatorcontrib>Mierke, Dale F</creatorcontrib><creatorcontrib>Atwood, Walter J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Gee, Gretchen V</au><au>Tsomaia, Natia</au><au>Mierke, Dale F</au><au>Atwood, Walter J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modeling a Sialic Acid Binding Pocket in the External Loops of JC Virus VP1</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2004-11-19</date><risdate>2004</risdate><volume>279</volume><issue>47</issue><spage>49172</spage><epage>49176</epage><pages>49172-49176</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>JC virus (JCV) is a common human polyomavirus that infects over 70% of the population worldwide. JCV has a restricted cell
tropism that is caused partly by the initial interaction between the virus and sialic acid-containing host cell receptors.
To identify the molecular interactions between the virus and its cellular receptor, we used a combined approach of site-directed
mutagenesis and homology-based molecular modeling. A model of the major viral capsid protein VP1 based on sequence alignment
with other closely related polyomaviruses allowed us to target specific amino acids in the extracellular loops of VP1 for
mutagenesis. An analysis of the growth rates of 17 point mutants led to the identification of VP1 amino acids that are critical
in virus-host cell receptor interactions. Molecular dynamics simulations were then used to build and confirm a model of the
interaction between VP1 and the sialic acid component of the JCV receptor.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>15347668</pmid><doi>10.1074/jbc.M409326200</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2004-11, Vol.279 (47), p.49172-49176 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | ScienceDirect (Elsevier) |
| subjects | Binding Sites Capsid Capsid Proteins - chemistry Cell Line Cell Nucleus - virology Computer Simulation Fluorescent Antibody Technique, Indirect Humans JC virus Microscopy, Electron Models, Molecular Mutagenesis, Site-Directed N-Acetylneuraminic Acid - chemistry Neuroglia - cytology Neuroglia - virology Plasmids - metabolism Polyomavirus Protein Binding Protein Conformation Protein Structure, Tertiary Time Factors Transfection |
| title | Modeling a Sialic Acid Binding Pocket in the External Loops of JC Virus VP1 |
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