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Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA
GDP‐bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub‐cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP‐to‐GTP exchange. The dissociation of GDI from Rabs is believed to requ...
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Published in: | The EMBO journal 2010-01, Vol.29 (2), p.496-504 |
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creator | Suh, Hye-Young Lee, Dong-Won Lee, Kwang-Hoon Ku, Bonsu Choi, Sung-Jin Woo, Jae-Sung Kim, Yeon-Gil Oh, Byung-Ha |
description | GDP‐bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub‐cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP‐to‐GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA‐1 and
Legionella pneumophila
SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure‐based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein. |
doi_str_mv | 10.1038/emboj.2009.347 |
format | article |
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Legionella pneumophila
SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure‐based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2009.347</identifier><identifier>PMID: 19942850</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Amino Acid Sequence ; Bacterial Proteins - chemistry ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Catalysis ; Cellular biology ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; EMBO37 ; EMBO40 ; GDF ; GDI ; GEF ; Guanine Nucleotide Dissociation Inhibitors - metabolism ; Guanine Nucleotide Exchange Factors - chemistry ; Guanine Nucleotide Exchange Factors - genetics ; Guanine Nucleotide Exchange Factors - metabolism ; Guanosine Diphosphate - metabolism ; Guanosine Triphosphate - metabolism ; Humans ; Inhibitor drugs ; Legionella pneumophila ; Legionella pneumophila - metabolism ; Legionnaires' Disease - metabolism ; Liposomes - metabolism ; Magnesium - metabolism ; Models, Molecular ; Molecular biology ; Molecular Sequence Data ; Mutation ; p-Rab1 ; Point Mutation ; Protein Binding ; Protein Conformation ; rab1 GTP-Binding Proteins - metabolism ; rho-Specific Guanine Nucleotide Dissociation Inhibitors ; Sequence Alignment ; SidM/DrrA ; Substrate Specificity</subject><ispartof>The EMBO journal, 2010-01, Vol.29 (2), p.496-504</ispartof><rights>European Molecular Biology Organization 2010</rights><rights>Copyright © 2010 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Jan 20, 2010</rights><rights>Copyright © 2010, European Molecular Biology Organization 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6007-2f8815b14f81a2dd2085dd5b4e2b4d6354ca1c9eced2e18e1a1675b99915bcba3</citedby><cites>FETCH-LOGICAL-c6007-2f8815b14f81a2dd2085dd5b4e2b4d6354ca1c9eced2e18e1a1675b99915bcba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824451/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824451/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19942850$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suh, Hye-Young</creatorcontrib><creatorcontrib>Lee, Dong-Won</creatorcontrib><creatorcontrib>Lee, Kwang-Hoon</creatorcontrib><creatorcontrib>Ku, Bonsu</creatorcontrib><creatorcontrib>Choi, Sung-Jin</creatorcontrib><creatorcontrib>Woo, Jae-Sung</creatorcontrib><creatorcontrib>Kim, Yeon-Gil</creatorcontrib><creatorcontrib>Oh, Byung-Ha</creatorcontrib><title>Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>GDP‐bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub‐cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP‐to‐GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA‐1 and
Legionella pneumophila
SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure‐based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein.</description><subject>Amino Acid Sequence</subject><subject>Bacterial Proteins - chemistry</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Catalysis</subject><subject>Cellular biology</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>EMBO37</subject><subject>EMBO40</subject><subject>GDF</subject><subject>GDI</subject><subject>GEF</subject><subject>Guanine Nucleotide Dissociation Inhibitors - metabolism</subject><subject>Guanine Nucleotide Exchange Factors - chemistry</subject><subject>Guanine Nucleotide Exchange Factors - genetics</subject><subject>Guanine Nucleotide Exchange Factors - metabolism</subject><subject>Guanosine Diphosphate - metabolism</subject><subject>Guanosine Triphosphate - metabolism</subject><subject>Humans</subject><subject>Inhibitor drugs</subject><subject>Legionella pneumophila</subject><subject>Legionella pneumophila - metabolism</subject><subject>Legionnaires' Disease - metabolism</subject><subject>Liposomes - metabolism</subject><subject>Magnesium - metabolism</subject><subject>Models, Molecular</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>p-Rab1</subject><subject>Point Mutation</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>rab1 GTP-Binding Proteins - metabolism</subject><subject>rho-Specific Guanine Nucleotide Dissociation Inhibitors</subject><subject>Sequence Alignment</subject><subject>SidM/DrrA</subject><subject>Substrate Specificity</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkktvEzEUhUcIREthyxKNWMBqEl-PPY8NUpOWUJQCUngsjce-SZxOZoLtKc2_x-lEaUECVn595_heH0fRcyADIGkxxHXVrgaUkHKQsvxBdAwsIwklOX8YHROaQcKgKI-iJ86tCCG8yOFxdARlyWjByXH0feZtp3xnZR2bxpnF0rsw8W3slxjrLmw3naqx9UZjjDdqKZsFxrLR8eTsItbGbWqpcI2Nj6Xy5tr4bdzO45nRl8Mza0-fRo_msnb4bD-eRF_enn8ev0umHycX49NpojJC8oTOiwJ4BWxegKRaU1JwrXnFkFZMZylnSoIqUaGmCAWChCznVVmWQaUqmZ5Eb3rfTVetUatQUOhJbKxZS7sVrTTi95PGLMWivRa0oIxxCAav9wa2_dGh82JtnMK6lg22nRN5yiiDlBWBfPVPkkJKOMAOfPkHuGo724RnEFBymnFgaYAGPaRs65zF-aFmIGKXsbjNWOwyFiHjIHhxv9M7fB9qAPIe-Glq3P7HTpxfjt7vFr31sFe6IAo523sF_62YfYuNDJ8ID5fdYne2SQ8Z5_HmwEh7JbI8zbn49mEixjCajT59nQqe_gKrrt-p</recordid><startdate>20100120</startdate><enddate>20100120</enddate><creator>Suh, Hye-Young</creator><creator>Lee, Dong-Won</creator><creator>Lee, Kwang-Hoon</creator><creator>Ku, Bonsu</creator><creator>Choi, Sung-Jin</creator><creator>Woo, Jae-Sung</creator><creator>Kim, Yeon-Gil</creator><creator>Oh, Byung-Ha</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>Nature Publishing Group</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7T7</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100120</creationdate><title>Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA</title><author>Suh, Hye-Young ; Lee, Dong-Won ; Lee, Kwang-Hoon ; Ku, Bonsu ; Choi, Sung-Jin ; Woo, Jae-Sung ; Kim, Yeon-Gil ; Oh, Byung-Ha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6007-2f8815b14f81a2dd2085dd5b4e2b4d6354ca1c9eced2e18e1a1675b99915bcba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Sequence</topic><topic>Bacterial Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suh, Hye-Young</au><au>Lee, Dong-Won</au><au>Lee, Kwang-Hoon</au><au>Ku, Bonsu</au><au>Choi, Sung-Jin</au><au>Woo, Jae-Sung</au><au>Kim, Yeon-Gil</au><au>Oh, Byung-Ha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2010-01-20</date><risdate>2010</risdate><volume>29</volume><issue>2</issue><spage>496</spage><epage>504</epage><pages>496-504</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>GDP‐bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub‐cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP‐to‐GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA‐1 and
Legionella pneumophila
SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure‐based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>19942850</pmid><doi>10.1038/emboj.2009.347</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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source | Open Access: PubMed Central |
subjects | Amino Acid Sequence Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism Catalysis Cellular biology DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism EMBO37 EMBO40 GDF GDI GEF Guanine Nucleotide Dissociation Inhibitors - metabolism Guanine Nucleotide Exchange Factors - chemistry Guanine Nucleotide Exchange Factors - genetics Guanine Nucleotide Exchange Factors - metabolism Guanosine Diphosphate - metabolism Guanosine Triphosphate - metabolism Humans Inhibitor drugs Legionella pneumophila Legionella pneumophila - metabolism Legionnaires' Disease - metabolism Liposomes - metabolism Magnesium - metabolism Models, Molecular Molecular biology Molecular Sequence Data Mutation p-Rab1 Point Mutation Protein Binding Protein Conformation rab1 GTP-Binding Proteins - metabolism rho-Specific Guanine Nucleotide Dissociation Inhibitors Sequence Alignment SidM/DrrA Substrate Specificity |
title | Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA |
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