Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution
Infection by the four serotypes of Dengue virus (DENV‐1 to DENV‐4) causes an important arthropod‐borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA‐...
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| Veröffentlicht in: | Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2015-11, Vol.71 (11), p.2309-2327 |
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| creator | Saw, Wuan Geok Tria, Giancarlo Grüber, Ardina Subramanian Manimekalai, Malathy Sony Zhao, Yongqian Chandramohan, Arun Srinivasan Anand, Ganesh Matsui, Tsutomu Weiss, Thomas M. Vasudevan, Subhash G. Grüber, Gerhard |
| description | Infection by the four serotypes of Dengue virus (DENV‐1 to DENV‐4) causes an important arthropod‐borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA‐dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all four Dengue virus serotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full‐length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV‐1 to DENV‐4 NS5 forms are elongated and flexible in solution, with DENV‐4 NS5 being more compact relative to NS5 from DENV‐1, DENV‐2 and DENV‐3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten‐residue linker region to the flexibility of the entire NS5. Swapping the ten‐residue linker between DENV‐4 NS5FL and DENV‐3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented. |
| doi_str_mv | 10.1107/S1399004715017721 |
| format | Article |
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The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA‐dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all four Dengue virus serotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full‐length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV‐1 to DENV‐4 NS5 forms are elongated and flexible in solution, with DENV‐4 NS5 being more compact relative to NS5 from DENV‐1, DENV‐2 and DENV‐3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten‐residue linker region to the flexibility of the entire NS5. Swapping the ten‐residue linker between DENV‐4 NS5FL and DENV‐3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. 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Section D, Biological crystallography., 2015-11, Vol.71 (11), p.2309-2327</ispartof><rights>International Union of Crystallography, 2015</rights><rights>International Union of Crystallography 2015 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5650-9de5767ff945b49a6905ac65df789e67fa97a89456abe7da0cf779f6fb5ab1913</citedby><cites>FETCH-LOGICAL-c5650-9de5767ff945b49a6905ac65df789e67fa97a89456abe7da0cf779f6fb5ab1913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1107%2FS1399004715017721$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1107%2FS1399004715017721$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26527147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1257423$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Saw, Wuan Geok</creatorcontrib><creatorcontrib>Tria, Giancarlo</creatorcontrib><creatorcontrib>Grüber, Ardina</creatorcontrib><creatorcontrib>Subramanian Manimekalai, Malathy Sony</creatorcontrib><creatorcontrib>Zhao, Yongqian</creatorcontrib><creatorcontrib>Chandramohan, Arun</creatorcontrib><creatorcontrib>Srinivasan Anand, Ganesh</creatorcontrib><creatorcontrib>Matsui, Tsutomu</creatorcontrib><creatorcontrib>Weiss, Thomas M.</creatorcontrib><creatorcontrib>Vasudevan, Subhash G.</creatorcontrib><creatorcontrib>Grüber, Gerhard</creatorcontrib><creatorcontrib>SLAC National Accelerator Lab., Menlo Park, CA (United States)</creatorcontrib><title>Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution</title><title>Acta crystallographica. Section D, Biological crystallography.</title><addtitle>Acta Crystallographica D</addtitle><description>Infection by the four serotypes of Dengue virus (DENV‐1 to DENV‐4) causes an important arthropod‐borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA‐dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all four Dengue virus serotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full‐length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV‐1 to DENV‐4 NS5 forms are elongated and flexible in solution, with DENV‐4 NS5 being more compact relative to NS5 from DENV‐1, DENV‐2 and DENV‐3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten‐residue linker region to the flexibility of the entire NS5. Swapping the ten‐residue linker between DENV‐4 NS5FL and DENV‐3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented.</description><subject>Amino Acid Sequence</subject><subject>dengue</subject><subject>Dengue - virology</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Dengue Virus - chemistry</subject><subject>Deuterium</subject><subject>Elongation</subject><subject>flavivirus</subject><subject>Flexibility</subject><subject>Humans</subject><subject>Mathematical models</subject><subject>methyltransferase</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>nonstructural proteins</subject><subject>Protein Conformation</subject><subject>protein flexibility</subject><subject>Proteins</subject><subject>Replication</subject><subject>Research Papers</subject><subject>Ribonucleic acids</subject><subject>RNA polymerase</subject><subject>Scattering, Small Angle</subject><subject>Sequence Alignment</subject><subject>Serogroup</subject><subject>small-angle X-ray scattering</subject><subject>Viral diseases</subject><subject>Viral Nonstructural Proteins - chemistry</subject><subject>viral polymerase</subject><subject>X-Ray Diffraction</subject><issn>1399-0047</issn><issn>0907-4449</issn><issn>1399-0047</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk9vEzEQxVcIREvhA3BBFly4BGyv_6wvSFELKVIpSAEqTpbXGScuzjrYu6X59jjaEhU40JOteb_3LM9MVT0l-BUhWL6ek1opjJkkHBMpKblXHe5Kk13t_q37QfUo50uMMaW1fFgdUMGpJEweVmHep8H2QzIB-S775apHplsgF-DatwGQA1NUyCg6dD7naJNiD4VELsU1MiEgF4eEMpT6djNyJ9AtB0BXPg25pKIcw9D72D2uHjgTMjy5OY-qL-_efj4-nZx9nL0_np5NLBccT9QCuBTSOcV4y5QRCnNjBV842SgoglHSNEUUpgW5MNg6KZUTruWmJYrUR9WbMXcztGtYWOj68j-9SX5t0lZH4_WfSudXehmvNBM1Yc0u4PkYEHPvdba-B7uysevA9ppQLhmtC_Ty5pUUfwyQe7322UIIpoM4ZF0mgmtKuCR3QJlopGBM3QGtyxgJF7SgL_5CL8soutLZQlFFGszI7m0yUjbFnBO4fR8I1rs10v-sUfE8u93AveP33hRAjcBPH2D7_0Q9_XZCL6acYFy8k9Hrcw_Xe69J37WQteT64nymZ18_NfjDaa2b-heG6OHE</recordid><startdate>201511</startdate><enddate>201511</enddate><creator>Saw, Wuan Geok</creator><creator>Tria, Giancarlo</creator><creator>Grüber, Ardina</creator><creator>Subramanian Manimekalai, Malathy Sony</creator><creator>Zhao, Yongqian</creator><creator>Chandramohan, Arun</creator><creator>Srinivasan Anand, Ganesh</creator><creator>Matsui, Tsutomu</creator><creator>Weiss, Thomas M.</creator><creator>Vasudevan, Subhash G.</creator><creator>Grüber, Gerhard</creator><general>International Union of Crystallography</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7QP</scope><scope>7SP</scope><scope>7SR</scope><scope>7TK</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>H8D</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>201511</creationdate><title>Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution</title><author>Saw, Wuan Geok ; Tria, Giancarlo ; Grüber, Ardina ; Subramanian Manimekalai, Malathy Sony ; Zhao, Yongqian ; Chandramohan, Arun ; Srinivasan Anand, Ganesh ; Matsui, Tsutomu ; Weiss, Thomas M. ; Vasudevan, Subhash G. ; Grüber, Gerhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5650-9de5767ff945b49a6905ac65df789e67fa97a89456abe7da0cf779f6fb5ab1913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amino Acid Sequence</topic><topic>dengue</topic><topic>Dengue - virology</topic><topic>Dengue fever</topic><topic>Dengue virus</topic><topic>Dengue Virus - chemistry</topic><topic>Deuterium</topic><topic>Elongation</topic><topic>flavivirus</topic><topic>Flexibility</topic><topic>Humans</topic><topic>Mathematical models</topic><topic>methyltransferase</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>nonstructural proteins</topic><topic>Protein Conformation</topic><topic>protein flexibility</topic><topic>Proteins</topic><topic>Replication</topic><topic>Research Papers</topic><topic>Ribonucleic acids</topic><topic>RNA polymerase</topic><topic>Scattering, Small Angle</topic><topic>Sequence Alignment</topic><topic>Serogroup</topic><topic>small-angle X-ray scattering</topic><topic>Viral diseases</topic><topic>Viral Nonstructural Proteins - chemistry</topic><topic>viral polymerase</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saw, Wuan Geok</creatorcontrib><creatorcontrib>Tria, Giancarlo</creatorcontrib><creatorcontrib>Grüber, Ardina</creatorcontrib><creatorcontrib>Subramanian Manimekalai, Malathy Sony</creatorcontrib><creatorcontrib>Zhao, Yongqian</creatorcontrib><creatorcontrib>Chandramohan, Arun</creatorcontrib><creatorcontrib>Srinivasan Anand, Ganesh</creatorcontrib><creatorcontrib>Matsui, Tsutomu</creatorcontrib><creatorcontrib>Weiss, Thomas M.</creatorcontrib><creatorcontrib>Vasudevan, Subhash G.</creatorcontrib><creatorcontrib>Grüber, Gerhard</creatorcontrib><creatorcontrib>SLAC National Accelerator Lab., Menlo Park, CA (United States)</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Aerospace Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta crystallographica. Section D, Biological crystallography.</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saw, Wuan Geok</au><au>Tria, Giancarlo</au><au>Grüber, Ardina</au><au>Subramanian Manimekalai, Malathy Sony</au><au>Zhao, Yongqian</au><au>Chandramohan, Arun</au><au>Srinivasan Anand, Ganesh</au><au>Matsui, Tsutomu</au><au>Weiss, Thomas M.</au><au>Vasudevan, Subhash G.</au><au>Grüber, Gerhard</au><aucorp>SLAC National Accelerator Lab., Menlo Park, CA (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution</atitle><jtitle>Acta crystallographica. Section D, Biological crystallography.</jtitle><addtitle>Acta Crystallographica D</addtitle><date>2015-11</date><risdate>2015</risdate><volume>71</volume><issue>11</issue><spage>2309</spage><epage>2327</epage><pages>2309-2327</pages><issn>1399-0047</issn><issn>0907-4449</issn><eissn>1399-0047</eissn><abstract>Infection by the four serotypes of Dengue virus (DENV‐1 to DENV‐4) causes an important arthropod‐borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA‐dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all four Dengue virus serotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full‐length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV‐1 to DENV‐4 NS5 forms are elongated and flexible in solution, with DENV‐4 NS5 being more compact relative to NS5 from DENV‐1, DENV‐2 and DENV‐3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten‐residue linker region to the flexibility of the entire NS5. Swapping the ten‐residue linker between DENV‐4 NS5FL and DENV‐3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented.</abstract><cop>5 Abbey Square, Chester, Cheshire CH1 2HU, England</cop><pub>International Union of Crystallography</pub><pmid>26527147</pmid><doi>10.1107/S1399004715017721</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence dengue Dengue - virology Dengue fever Dengue virus Dengue Virus - chemistry Deuterium Elongation flavivirus Flexibility Humans Mathematical models methyltransferase Models, Molecular Molecular Sequence Data nonstructural proteins Protein Conformation protein flexibility Proteins Replication Research Papers Ribonucleic acids RNA polymerase Scattering, Small Angle Sequence Alignment Serogroup small-angle X-ray scattering Viral diseases Viral Nonstructural Proteins - chemistry viral polymerase X-Ray Diffraction |
| title | Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution |
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