Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface
Identifieur interne : 001256 ( Main/Exploration ); précédent : 001255; suivant : 001257Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface
Auteurs : Guoliang Lu [République populaire de Chine] ; Peng Gong [République populaire de Chine]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2013.
Abstract
The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.
Url:
DOI: 10.1371/journal.ppat.1003549
PubMed: 23950717
PubMed Central: 3738499
Affiliations:
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China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>University of Chinese Academy of Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gong, Peng" sort="Gong, Peng" uniqKey="Gong P" first="Peng" last="Gong">Peng Gong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuchang District, Wuhan, Hubei, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuchang District, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno 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One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cleaves, Gr" uniqKey="Cleaves G">GR Cleaves</name></author><author><name sortKey="Dubin, Dt" uniqKey="Dubin D">DT Dubin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Egloff, Mp" uniqKey="Egloff M">MP Egloff</name></author><author><name sortKey="Benarroch, D" uniqKey="Benarroch D">D Benarroch</name></author><author><name sortKey="Selisko, B" uniqKey="Selisko B">B Selisko</name></author><author><name sortKey="Romette, Jl" uniqKey="Romette J">JL Romette</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B Canard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, L" uniqKey="Liu L">L 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Gong</name></author><author><name sortKey="Martin, Ct" uniqKey="Martin C">CT Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mosley, Rt" uniqKey="Mosley R">RT Mosley</name></author><author><name sortKey="Edwards, Te" uniqKey="Edwards T">TE Edwards</name></author><author><name sortKey="Murakami, E" uniqKey="Murakami E">E Murakami</name></author><author><name sortKey="Lam, Am" uniqKey="Lam A">AM Lam</name></author><author><name sortKey="Grice, Rl" uniqKey="Grice R">RL Grice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Z" uniqKey="Jin Z">Z Jin</name></author><author><name sortKey="Leveque, V" uniqKey="Leveque V">V Leveque</name></author><author><name sortKey="Ma, H" uniqKey="Ma H">H Ma</name></author><author><name sortKey="Johnson, Ka" uniqKey="Johnson K">KA Johnson</name></author><author><name sortKey="Klumpp, K" uniqKey="Klumpp K">K Klumpp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gohara, Dw" uniqKey="Gohara D">DW Gohara</name></author><author><name sortKey="Ha, Cs" uniqKey="Ha C">CS Ha</name></author><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author><author><name sortKey="Ghosh, B" uniqKey="Ghosh B">B Ghosh</name></author><author><name sortKey="Arnold, Jj" uniqKey="Arnold J">JJ Arnold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pflugrath, Jw" uniqKey="Pflugrath J">JW Pflugrath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccoy, Aj" uniqKey="Mccoy A">AJ McCoy</name></author><author><name sortKey="Grosse Kunstleve, Rw" uniqKey="Grosse Kunstleve R">RW Grosse-Kunstleve</name></author><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Winn, Md" uniqKey="Winn M">MD Winn</name></author><author><name sortKey="Storoni, Lc" uniqKey="Storoni L">LC Storoni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P Emsley</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Grosse Kunstleve, Rw" uniqKey="Grosse Kunstleve R">RW Grosse-Kunstleve</name></author><author><name sortKey="Hung, Lw" uniqKey="Hung L">LW Hung</name></author><author><name sortKey="Ioerger, Tr" uniqKey="Ioerger T">TR Ioerger</name></author><author><name sortKey="Mccoy, Aj" uniqKey="Mccoy A">AJ McCoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brunger, At" uniqKey="Brunger A">AT Brunger</name></author><author><name sortKey="Adams, Pd" uniqKey="Adams P">PD Adams</name></author><author><name sortKey="Clore, Gm" uniqKey="Clore G">GM Clore</name></author><author><name sortKey="Delano, Wl" uniqKey="Delano W">WL DeLano</name></author><author><name sortKey="Gros, P" uniqKey="Gros P">P Gros</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Lu, Guoliang" sort="Lu, Guoliang" uniqKey="Lu G" first="Guoliang" last="Lu">Guoliang Lu</name></noRegion><name sortKey="Gong, Peng" sort="Gong, Peng" uniqKey="Gong P" first="Peng" last="Gong">Peng Gong</name><name sortKey="Lu, Guoliang" sort="Lu, Guoliang" uniqKey="Lu G" first="Guoliang" last="Lu">Guoliang Lu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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