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Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis
The pathogenic pathway of Legionella pneumophila exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzy...
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| Published in: | Scientific reports 2016-01, Vol.6 (1), p.19896-19896, Article 19896 |
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| creator | Luitz, Manuel P. Bomblies, Rainer Ramcke, Evelyn Itzen, Aymelt Zacharias, Martin |
| description | The pathogenic pathway of
Legionella pneumophila
exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins. |
| doi_str_mv | 10.1038/srep19896 |
| format | article |
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Legionella pneumophila
exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep19896</identifier><identifier>PMID: 26818796</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/57/2266 ; 631/57/2272/2273 ; 82/80 ; 82/83 ; Adenine ; Adenosine ; Adenosine Monophosphate - chemistry ; Adenosine Monophosphate - metabolism ; AMP ; Binding sites ; Conformation ; Crystal structure ; Electrostatic properties ; Guanosine triphosphatases ; Guanosine triphosphate ; Guanosine Triphosphate - chemistry ; Guanosine Triphosphate - metabolism ; Humanities and Social Sciences ; Molecular dynamics ; Molecular Dynamics Simulation ; multidisciplinary ; Protein Binding ; Protein Conformation ; Protein Stability ; Proteins ; rab1 GTP-Binding Proteins - chemistry ; rab1 GTP-Binding Proteins - metabolism ; Ras protein ; Science ; Simulation ; Simulation analysis ; Static Electricity ; Tyrosine - chemistry ; Tyrosine - metabolism</subject><ispartof>Scientific reports, 2016-01, Vol.6 (1), p.19896-19896, Article 19896</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jan 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-a0ec33dd9d738565f9f31e9b321b369eee615e46b65ab66894e630ad7b55ed023</citedby><cites>FETCH-LOGICAL-c438t-a0ec33dd9d738565f9f31e9b321b369eee615e46b65ab66894e630ad7b55ed023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1899046435/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1899046435?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26818796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luitz, Manuel P.</creatorcontrib><creatorcontrib>Bomblies, Rainer</creatorcontrib><creatorcontrib>Ramcke, Evelyn</creatorcontrib><creatorcontrib>Itzen, Aymelt</creatorcontrib><creatorcontrib>Zacharias, Martin</creatorcontrib><title>Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The pathogenic pathway of
Legionella pneumophila
exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins.</description><subject>631/57/2266</subject><subject>631/57/2272/2273</subject><subject>82/80</subject><subject>82/83</subject><subject>Adenine</subject><subject>Adenosine</subject><subject>Adenosine Monophosphate - chemistry</subject><subject>Adenosine Monophosphate - metabolism</subject><subject>AMP</subject><subject>Binding sites</subject><subject>Conformation</subject><subject>Crystal structure</subject><subject>Electrostatic properties</subject><subject>Guanosine triphosphatases</subject><subject>Guanosine triphosphate</subject><subject>Guanosine Triphosphate - chemistry</subject><subject>Guanosine Triphosphate - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>multidisciplinary</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Protein Stability</subject><subject>Proteins</subject><subject>rab1 GTP-Binding Proteins - chemistry</subject><subject>rab1 GTP-Binding Proteins - metabolism</subject><subject>Ras protein</subject><subject>Science</subject><subject>Simulation</subject><subject>Simulation analysis</subject><subject>Static Electricity</subject><subject>Tyrosine - chemistry</subject><subject>Tyrosine - metabolism</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNplkV1rFDEUhoMottRe-Ack4I0Kq_meiRfCUrQtFBRZr0Myc6amZpI1mSmMv96UXZdVQyAHzsNzTngRek7JW0p4-65k2FLdavUInTIi5Ipxxh4f1SfovJQ7Uo9kWlD9FJ0w1dK20eoU_Vj3EJewBDv5FHEa8GbJTYPLZJ0P_hcU_NU66vDl5ostgH3Ett5u8vfwAE3wHq_xmAJ0c7AZ90u0o-8KLn6c91IbbViKL8_Qk8GGAuf79wx9-_Rxc3G1uvl8eX2xvll1grfTyhLoOO973Te8lUoOeuAUtOOMOq40ACgqQSinpHVKtVqA4sT2jZMSesL4Gfqw825nN0LfQZyyDWab_WjzYpL15u9O9N_Nbbo3ouGEMVEFr_aCnH7OUCYz-tJBCDZCmouhjaJCMdLSir78B71Lc64frlSrNRFKcFmp1zuqy6nUwIbDMpSYhxTNIcXKvjje_kD-yawCb3ZAqa14C_lo5H-23_Lupz8</recordid><startdate>20160128</startdate><enddate>20160128</enddate><creator>Luitz, Manuel P.</creator><creator>Bomblies, Rainer</creator><creator>Ramcke, Evelyn</creator><creator>Itzen, Aymelt</creator><creator>Zacharias, Martin</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160128</creationdate><title>Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis</title><author>Luitz, Manuel P. ; Bomblies, Rainer ; Ramcke, Evelyn ; Itzen, Aymelt ; Zacharias, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-a0ec33dd9d738565f9f31e9b321b369eee615e46b65ab66894e630ad7b55ed023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/57/2266</topic><topic>631/57/2272/2273</topic><topic>82/80</topic><topic>82/83</topic><topic>Adenine</topic><topic>Adenosine</topic><topic>Adenosine Monophosphate - chemistry</topic><topic>Adenosine Monophosphate - metabolism</topic><topic>AMP</topic><topic>Binding sites</topic><topic>Conformation</topic><topic>Crystal structure</topic><topic>Electrostatic properties</topic><topic>Guanosine triphosphatases</topic><topic>Guanosine triphosphate</topic><topic>Guanosine Triphosphate - chemistry</topic><topic>Guanosine Triphosphate - metabolism</topic><topic>Humanities and Social Sciences</topic><topic>Molecular dynamics</topic><topic>Molecular Dynamics Simulation</topic><topic>multidisciplinary</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Protein Stability</topic><topic>Proteins</topic><topic>rab1 GTP-Binding Proteins - chemistry</topic><topic>rab1 GTP-Binding Proteins - metabolism</topic><topic>Ras protein</topic><topic>Science</topic><topic>Simulation</topic><topic>Simulation analysis</topic><topic>Static Electricity</topic><topic>Tyrosine - chemistry</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luitz, Manuel P.</creatorcontrib><creatorcontrib>Bomblies, Rainer</creatorcontrib><creatorcontrib>Ramcke, Evelyn</creatorcontrib><creatorcontrib>Itzen, Aymelt</creatorcontrib><creatorcontrib>Zacharias, Martin</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luitz, Manuel P.</au><au>Bomblies, Rainer</au><au>Ramcke, Evelyn</au><au>Itzen, Aymelt</au><au>Zacharias, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-01-28</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>19896</spage><epage>19896</epage><pages>19896-19896</pages><artnum>19896</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The pathogenic pathway of
Legionella pneumophila
exploits the intercellular vesicle transport system via the posttranslational attachment of adenosine monophosphate (AMP) to the Tyr77 sidechain of human Ras like GTPase Rab1b. The modification, termed adenylylation, is performed by the bacterial enzyme DrrA/SidM, however the effect on conformational properties of the molecular switch mechanism of Rab1b remained unresolved. In this study we find that the adenylylation of Tyr77 stabilizes the active Rab1b state by locking the switch in the active signaling conformation independent of bound GTP or GDP and that electrostatic interactions due to the additional negative charge in the switch region make significant contributions. The stacking interaction between adenine and Phe45 however, seems to have only minor influence on this stabilisation. The results may also have implications for the mechanistic understanding of conformational switching in other signaling proteins.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26818796</pmid><doi>10.1038/srep19896</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/57/2266 631/57/2272/2273 82/80 82/83 Adenine Adenosine Adenosine Monophosphate - chemistry Adenosine Monophosphate - metabolism AMP Binding sites Conformation Crystal structure Electrostatic properties Guanosine triphosphatases Guanosine triphosphate Guanosine Triphosphate - chemistry Guanosine Triphosphate - metabolism Humanities and Social Sciences Molecular dynamics Molecular Dynamics Simulation multidisciplinary Protein Binding Protein Conformation Protein Stability Proteins rab1 GTP-Binding Proteins - chemistry rab1 GTP-Binding Proteins - metabolism Ras protein Science Simulation Simulation analysis Static Electricity Tyrosine - chemistry Tyrosine - metabolism |
| title | Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis |
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