Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity
Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs. PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction. Using site‐directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD...
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| Veröffentlicht in: | The EMBO journal 1997-08, Vol.16 (15), p.4519-4530 |
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| container_title | The EMBO journal |
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| creator | Sung, Tsung-Chang Roper, Rachel L. Zhang, Yue Rudge, Simon A. Temel, Ryan Hammond, Scott M. Morris, Andrew J. Moss, Bernard Engebrecht, JoAnne Frohman, Michael A. |
| description | Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs. PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction. Using site‐directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD1) and characterized. We find that a motif (HxKxxxxD) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism. Functional analysis of catalytically inactive point mutants for yeast PLD demonstrates that the meiotic phenotype ensuing from PLD deficiency in yeast derives from a loss of enzymatic activity. Finally, mutation of an HxKxxxxD motif found in a vaccinia viral protein expressed in the Golgi complex results in loss of efficient vaccinia virus cell‐to‐cell spreading, implicating the viral protein as a member of the superfamily and suggesting that it encodes a lipid modifying or binding activity. The results suggest that vaccinia virus and hPLD1 may act through analogous mechanisms to effect viral cellular egress and vesicular trafficking, respectively. |
| doi_str_mv | 10.1093/emboj/16.15.4519 |
| format | Article |
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PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction. Using site‐directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD1) and characterized. We find that a motif (HxKxxxxD) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism. Functional analysis of catalytically inactive point mutants for yeast PLD demonstrates that the meiotic phenotype ensuing from PLD deficiency in yeast derives from a loss of enzymatic activity. Finally, mutation of an HxKxxxxD motif found in a vaccinia viral protein expressed in the Golgi complex results in loss of efficient vaccinia virus cell‐to‐cell spreading, implicating the viral protein as a member of the superfamily and suggesting that it encodes a lipid modifying or binding activity. The results suggest that vaccinia virus and hPLD1 may act through analogous mechanisms to effect viral cellular egress and vesicular trafficking, respectively.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/16.15.4519</identifier><identifier>PMID: 9303296</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Amino Acid Sequence ; Animals ; Binding Sites - genetics ; Catalysis ; Conserved Sequence ; COS Cells ; Evolution, Molecular ; Humans ; Lysine - genetics ; Models, Biological ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; phospholipase D (PLD) ; Phospholipase D - genetics ; Point Mutation ; Saccharomyces cerevisiae - enzymology ; Saccharomyces cerevisiae - genetics ; Sequence Homology, Amino Acid ; SPO14 ; vaccinia virus ; Vaccinia virus - enzymology ; Vaccinia virus - genetics ; Vaccinia virus - pathogenicity ; Viral Proteins - genetics ; VP37</subject><ispartof>The EMBO journal, 1997-08, Vol.16 (15), p.4519-4530</ispartof><rights>Copyright © 1997 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5320-4aa56bc8436faffdaaf6f5a6f59a6eca94478576fba19db2585a838b4942358c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1170078/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1170078/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,1418,1434,27929,27930,45579,45580,46414,46838,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9303296$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sung, Tsung-Chang</creatorcontrib><creatorcontrib>Roper, Rachel L.</creatorcontrib><creatorcontrib>Zhang, Yue</creatorcontrib><creatorcontrib>Rudge, Simon A.</creatorcontrib><creatorcontrib>Temel, Ryan</creatorcontrib><creatorcontrib>Hammond, Scott M.</creatorcontrib><creatorcontrib>Morris, Andrew J.</creatorcontrib><creatorcontrib>Moss, Bernard</creatorcontrib><creatorcontrib>Engebrecht, JoAnne</creatorcontrib><creatorcontrib>Frohman, Michael A.</creatorcontrib><title>Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><description>Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs. PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction. Using site‐directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD1) and characterized. We find that a motif (HxKxxxxD) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism. Functional analysis of catalytically inactive point mutants for yeast PLD demonstrates that the meiotic phenotype ensuing from PLD deficiency in yeast derives from a loss of enzymatic activity. Finally, mutation of an HxKxxxxD motif found in a vaccinia viral protein expressed in the Golgi complex results in loss of efficient vaccinia virus cell‐to‐cell spreading, implicating the viral protein as a member of the superfamily and suggesting that it encodes a lipid modifying or binding activity. The results suggest that vaccinia virus and hPLD1 may act through analogous mechanisms to effect viral cellular egress and vesicular trafficking, respectively.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Binding Sites - genetics</subject><subject>Catalysis</subject><subject>Conserved Sequence</subject><subject>COS Cells</subject><subject>Evolution, Molecular</subject><subject>Humans</subject><subject>Lysine - genetics</subject><subject>Models, Biological</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>phospholipase D (PLD)</subject><subject>Phospholipase D - genetics</subject><subject>Point Mutation</subject><subject>Saccharomyces cerevisiae - enzymology</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Sequence Homology, Amino Acid</subject><subject>SPO14</subject><subject>vaccinia virus</subject><subject>Vaccinia virus - enzymology</subject><subject>Vaccinia virus - genetics</subject><subject>Vaccinia virus - pathogenicity</subject><subject>Viral Proteins - genetics</subject><subject>VP37</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EKkvhzgXJJ27Z2ok_4gsSlLIFtUVFoHKzJom965LEqZ2U7qV_Oy67CnDiMBppfvPejPQQeknJkhJVHJmu8tdHVCwpXzJO1SO0oEyQLCeSP0YLkguaMVqqp-hZjNeEEF5KeoAOVEGKXIkFuj-fRlib3kQXsbd42PiYqnUDRIPf48ZYlyAGHKfBBAuda7fY9XU7Na5fp_kYoI_Zyrdrh29dgBYPwY_G9TiYm8kF02DrAx78XaJTxAOMG58uutqN2-foiYU2mhf7foi-fTj5enyanX1efTx-e5bVvMhJxgC4qOqSFcKCtQ2AFZZDKgXC1KAYkyWXwlZAVVPlvORQFmXFFMsLXtbFIXqz8x2mqjNNbfr0dquH4DoIW-3B6X9J7zZ67W81pZIQWSaD13uD4G8mE0fduVibtoXe-ClqKnLBBc3TItkt1sHHGIydj1CiHzLTvzNLAk25fsgsSV79_dws2IeUuNrxn6412__66ZPzd58kV4Ql_ezdwzgFM4v_8GzHXRzN3Ywh_NBCFpLrq4uVvvpySS--s0sti1_-icMc</recordid><startdate>19970801</startdate><enddate>19970801</enddate><creator>Sung, Tsung-Chang</creator><creator>Roper, Rachel L.</creator><creator>Zhang, Yue</creator><creator>Rudge, Simon A.</creator><creator>Temel, Ryan</creator><creator>Hammond, Scott M.</creator><creator>Morris, Andrew J.</creator><creator>Moss, Bernard</creator><creator>Engebrecht, JoAnne</creator><creator>Frohman, Michael A.</creator><general>John Wiley & Sons, Ltd</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>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>19970801</creationdate><title>Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity</title><author>Sung, Tsung-Chang ; Roper, Rachel L. ; Zhang, Yue ; Rudge, Simon A. ; Temel, Ryan ; Hammond, Scott M. ; Morris, Andrew J. ; Moss, Bernard ; Engebrecht, JoAnne ; Frohman, Michael A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5320-4aa56bc8436faffdaaf6f5a6f59a6eca94478576fba19db2585a838b4942358c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Binding Sites - genetics</topic><topic>Catalysis</topic><topic>Conserved Sequence</topic><topic>COS Cells</topic><topic>Evolution, Molecular</topic><topic>Humans</topic><topic>Lysine - genetics</topic><topic>Models, Biological</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>phospholipase D (PLD)</topic><topic>Phospholipase D - genetics</topic><topic>Point Mutation</topic><topic>Saccharomyces cerevisiae - enzymology</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Sequence Homology, Amino Acid</topic><topic>SPO14</topic><topic>vaccinia virus</topic><topic>Vaccinia virus - enzymology</topic><topic>Vaccinia virus - genetics</topic><topic>Vaccinia virus - pathogenicity</topic><topic>Viral Proteins - genetics</topic><topic>VP37</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sung, Tsung-Chang</creatorcontrib><creatorcontrib>Roper, Rachel L.</creatorcontrib><creatorcontrib>Zhang, Yue</creatorcontrib><creatorcontrib>Rudge, Simon A.</creatorcontrib><creatorcontrib>Temel, Ryan</creatorcontrib><creatorcontrib>Hammond, Scott M.</creatorcontrib><creatorcontrib>Morris, Andrew J.</creatorcontrib><creatorcontrib>Moss, Bernard</creatorcontrib><creatorcontrib>Engebrecht, JoAnne</creatorcontrib><creatorcontrib>Frohman, Michael A.</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>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</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>Sung, Tsung-Chang</au><au>Roper, Rachel L.</au><au>Zhang, Yue</au><au>Rudge, Simon A.</au><au>Temel, Ryan</au><au>Hammond, Scott M.</au><au>Morris, Andrew J.</au><au>Moss, Bernard</au><au>Engebrecht, JoAnne</au><au>Frohman, Michael A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity</atitle><jtitle>The EMBO journal</jtitle><addtitle>EMBO J</addtitle><date>1997-08-01</date><risdate>1997</risdate><volume>16</volume><issue>15</issue><spage>4519</spage><epage>4530</epage><pages>4519-4530</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><abstract>Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs. PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction. Using site‐directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD1) and characterized. We find that a motif (HxKxxxxD) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism. Functional analysis of catalytically inactive point mutants for yeast PLD demonstrates that the meiotic phenotype ensuing from PLD deficiency in yeast derives from a loss of enzymatic activity. Finally, mutation of an HxKxxxxD motif found in a vaccinia viral protein expressed in the Golgi complex results in loss of efficient vaccinia virus cell‐to‐cell spreading, implicating the viral protein as a member of the superfamily and suggesting that it encodes a lipid modifying or binding activity. The results suggest that vaccinia virus and hPLD1 may act through analogous mechanisms to effect viral cellular egress and vesicular trafficking, respectively.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>9303296</pmid><doi>10.1093/emboj/16.15.4519</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0261-4189 |
| ispartof | The EMBO journal, 1997-08, Vol.16 (15), p.4519-4530 |
| issn | 0261-4189 1460-2075 1460-2075 |
| language | eng |
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| source | Wiley-Blackwell Journals; PubMed Central (Open access); MEDLINE; Wiley Online Library Journals; Full-Text Journals in Chemistry (Open access); EZB Electronic Journals Library |
| subjects | Amino Acid Sequence Animals Binding Sites - genetics Catalysis Conserved Sequence COS Cells Evolution, Molecular Humans Lysine - genetics Models, Biological Molecular Sequence Data Mutagenesis, Site-Directed phospholipase D (PLD) Phospholipase D - genetics Point Mutation Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae - genetics Sequence Homology, Amino Acid SPO14 vaccinia virus Vaccinia virus - enzymology Vaccinia virus - genetics Vaccinia virus - pathogenicity Viral Proteins - genetics VP37 |
| title | Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity |
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