Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.
Identifieur interne : 001013 ( Main/Exploration ); précédent : 001012; suivant : 001014Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.
Auteurs : Melanie J. Shears [Australie] ; James I. Macrae [Royaume-Uni] ; Vanessa Mollard [Australie] ; Christopher D. Goodman [Australie] ; Angelika Sturm [Australie] ; Lindsey M. Orchard [États-Unis] ; Manuel Llinás [États-Unis] ; Malcolm J. Mcconville [Australie] ; Cyrille Y. Botté [France] ; Geoffrey I. Mcfadden [Australie]Source :
- Cellular microbiology [ 1462-5822 ] ; 2017.
Descripteurs français
- KwdFr :
- Acides gras (métabolisme), Analyse de mutations d'ADN, Apicoplastes (enzymologie), Apicoplastes (métabolisme), Bactéries (génétique), Bactéries (métabolisme), Glycerol 3-phosphate acyltransferase (métabolisme), Plasmodium berghei (enzymologie), Plasmodium berghei (métabolisme), Plasmodium falciparum (enzymologie), Plasmodium falciparum (génétique), Plasmodium falciparum (métabolisme), Techniques de knock-out de gènes, Test de complémentation, Transport de protéines.
- MESH :
- enzymologie : Apicoplastes, Plasmodium berghei, Plasmodium falciparum.
- génétique : Bactéries, Plasmodium falciparum.
- métabolisme : Acides gras, Apicoplastes, Bactéries, Glycerol 3-phosphate acyltransferase, Plasmodium berghei, Plasmodium falciparum.
- Analyse de mutations d'ADN, Techniques de knock-out de gènes, Test de complémentation, Transport de protéines.
English descriptors
- KwdEn :
- Apicoplasts (enzymology), Apicoplasts (metabolism), Bacteria (genetics), Bacteria (metabolism), DNA Mutational Analysis, Fatty Acids (metabolism), Gene Knockout Techniques, Genetic Complementation Test, Glycerol-3-Phosphate O-Acyltransferase (metabolism), Plasmodium berghei (enzymology), Plasmodium berghei (metabolism), Plasmodium falciparum (enzymology), Plasmodium falciparum (genetics), Plasmodium falciparum (metabolism), Protein Transport.
- MESH :
- chemical , metabolism : Fatty Acids, Glycerol-3-Phosphate O-Acyltransferase.
- enzymology : Apicoplasts, Plasmodium berghei, Plasmodium falciparum.
- genetics : Bacteria, Plasmodium falciparum.
- metabolism : Apicoplasts, Bacteria, Plasmodium berghei, Plasmodium falciparum.
- DNA Mutational Analysis, Gene Knockout Techniques, Genetic Complementation Test, Protein Transport.
Abstract
Malaria parasites can synthesize fatty acids via a type II fatty acid synthesis (FASII) pathway located in their apicoplast. The FASII pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. Here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of FASII in human (Plasmodium falciparum) and rodent (Plasmodium berghei) malaria parasites and investigate how this enzyme contributes to incorporating FASII fatty acids into precursors for membrane lipid synthesis. Apicoplast targeting of the P. falciparum and P. berghei enzymes are confirmed by fusion of the N-terminal targeting sequence to GFP and 3' tagging of the full length protein. Activity of the P. falciparum enzyme is demonstrated by complementation in mutant bacteria, and critical residues in the putative active site identified by site-directed mutagenesis. Genetic disruption of the P. falciparum enzyme demonstrates it is dispensable in blood stage parasites, even in conditions known to induce FASII activity. Disruption of the P. berghei enzyme demonstrates it is dispensable in blood and mosquito stage parasites, and only essential for development in the late liver stage, consistent with the requirement for FASII in rodent malaria models. However, the P. berghei mutant liver stage phenotype is found to only partially phenocopy loss of FASII, suggesting newly made fatty acids can take multiple pathways out of the apicoplast and so giving new insight into the role of FASII and apicoplast glycerol 3-phosphate acyltransferase in malaria parasites.
DOI: 10.1111/cmi.12633
PubMed: 27324409
Affiliations:
- Australie, France, Royaume-Uni, États-Unis
- Auvergne-Rhône-Alpes, Pennsylvanie, Rhône-Alpes, Victoria (État)
- Grenoble, Melbourne, University Park (Pennsylvanie)
- Université Grenoble-Alpes, Université d'État de Pennsylvanie, Université de Melbourne
Links toward previous steps (curation, corpus...)
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- to stream Ncbi, to step Merge: 003734
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Le document en format XML
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Shears</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, VIC 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne, VIC 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Macrae, James I" sort="Macrae, James I" uniqKey="Macrae J" first="James I" last="Macrae">James I. Macrae</name><affiliation wicri:level="1"><nlm:affiliation>The Francis Crick Institute, Metabolomics, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The Francis Crick Institute, Metabolomics, The Ridgeway, Mill Hill, London, NW7 1AA</wicri:regionArea><wicri:noRegion>NW7 1AA</wicri:noRegion></affiliation></author><author><name sortKey="Mollard, Vanessa" sort="Mollard, Vanessa" uniqKey="Mollard V" first="Vanessa" last="Mollard">Vanessa Mollard</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, VIC 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne, VIC 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Goodman, Christopher D" sort="Goodman, Christopher D" uniqKey="Goodman C" first="Christopher D" last="Goodman">Christopher D. Goodman</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, VIC 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne, VIC 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Sturm, Angelika" sort="Sturm, Angelika" uniqKey="Sturm A" first="Angelika" last="Sturm">Angelika Sturm</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, VIC 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne, VIC 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Orchard, Lindsey M" sort="Orchard, Lindsey M" uniqKey="Orchard L" first="Lindsey M" last="Orchard">Lindsey M. Orchard</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, University Park, PA, 16802, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, University Park, PA, 16802</wicri:regionArea><orgName type="university">Université d'État de Pennsylvanie</orgName><placeName><settlement type="city">University Park (Pennsylvanie)</settlement><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Llinas, Manuel" sort="Llinas, Manuel" uniqKey="Llinas M" first="Manuel" last="Llinás">Manuel Llinás</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, University Park, PA, 16802, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, University Park, PA, 16802</wicri:regionArea><orgName type="university">Université d'État de Pennsylvanie</orgName><placeName><settlement type="city">University Park (Pennsylvanie)</settlement><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Mcconville, Malcolm J" sort="Mcconville, Malcolm J" uniqKey="Mcconville M" first="Malcolm J" last="Mcconville">Malcolm J. Mcconville</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Botte, Cyrille Y" sort="Botte, Cyrille Y" uniqKey="Botte C" first="Cyrille Y" last="Botté">Cyrille Y. Botté</name><affiliation wicri:level="4"><nlm:affiliation>Apicolipid team, Institute for Advanced Biosciences UMR CNRS5309 INSMERM U1209, Université Grenoble Alpes, Grenoble, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Apicolipid team, Institute for Advanced Biosciences UMR CNRS5309 INSMERM U1209, Université Grenoble Alpes, Grenoble</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement><settlement type="city">Grenoble</settlement></placeName><orgName type="university">Université Grenoble-Alpes</orgName></affiliation></author><author><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I" last="Mcfadden">Geoffrey I. Mcfadden</name><affiliation wicri:level="4"><nlm:affiliation>School of BioSciences, University of Melbourne, VIC 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of BioSciences, University of Melbourne, VIC 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><series><title level="j">Cellular microbiology</title><idno type="eISSN">1462-5822</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apicoplasts (enzymology)</term><term>Apicoplasts (metabolism)</term><term>Bacteria (genetics)</term><term>Bacteria (metabolism)</term><term>DNA Mutational Analysis</term><term>Fatty Acids (metabolism)</term><term>Gene Knockout Techniques</term><term>Genetic Complementation Test</term><term>Glycerol-3-Phosphate O-Acyltransferase (metabolism)</term><term>Plasmodium berghei (enzymology)</term><term>Plasmodium berghei (metabolism)</term><term>Plasmodium falciparum (enzymology)</term><term>Plasmodium falciparum (genetics)</term><term>Plasmodium falciparum (metabolism)</term><term>Protein Transport</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides gras (métabolisme)</term><term>Analyse de mutations d'ADN</term><term>Apicoplastes (enzymologie)</term><term>Apicoplastes (métabolisme)</term><term>Bactéries (génétique)</term><term>Bactéries (métabolisme)</term><term>Glycerol 3-phosphate acyltransferase (métabolisme)</term><term>Plasmodium berghei (enzymologie)</term><term>Plasmodium berghei (métabolisme)</term><term>Plasmodium falciparum (enzymologie)</term><term>Plasmodium falciparum (génétique)</term><term>Plasmodium falciparum (métabolisme)</term><term>Techniques de knock-out de gènes</term><term>Test de complémentation</term><term>Transport de protéines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Fatty Acids</term><term>Glycerol-3-Phosphate O-Acyltransferase</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Apicoplastes</term><term>Plasmodium berghei</term><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Apicoplasts</term><term>Plasmodium berghei</term><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Bacteria</term><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Bactéries</term><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Apicoplasts</term><term>Bacteria</term><term>Plasmodium berghei</term><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acides gras</term><term>Apicoplastes</term><term>Bactéries</term><term>Glycerol 3-phosphate acyltransferase</term><term>Plasmodium berghei</term><term>Plasmodium falciparum</term></keywords><keywords scheme="MESH" xml:lang="en"><term>DNA Mutational Analysis</term><term>Gene Knockout Techniques</term><term>Genetic Complementation Test</term><term>Protein Transport</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de mutations d'ADN</term><term>Techniques de knock-out de gènes</term><term>Test de complémentation</term><term>Transport de protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Malaria parasites can synthesize fatty acids via a type II fatty acid synthesis (FASII) pathway located in their apicoplast. The FASII pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. Here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of FASII in human (Plasmodium falciparum) and rodent (Plasmodium berghei) malaria parasites and investigate how this enzyme contributes to incorporating FASII fatty acids into precursors for membrane lipid synthesis. Apicoplast targeting of the P. falciparum and P. berghei enzymes are confirmed by fusion of the N-terminal targeting sequence to GFP and 3' tagging of the full length protein. Activity of the P. falciparum enzyme is demonstrated by complementation in mutant bacteria, and critical residues in the putative active site identified by site-directed mutagenesis. Genetic disruption of the P. falciparum enzyme demonstrates it is dispensable in blood stage parasites, even in conditions known to induce FASII activity. Disruption of the P. berghei enzyme demonstrates it is dispensable in blood and mosquito stage parasites, and only essential for development in the late liver stage, consistent with the requirement for FASII in rodent malaria models. However, the P. berghei mutant liver stage phenotype is found to only partially phenocopy loss of FASII, suggesting newly made fatty acids can take multiple pathways out of the apicoplast and so giving new insight into the role of FASII and apicoplast glycerol 3-phosphate acyltransferase in malaria parasites.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Pennsylvanie</li><li>Rhône-Alpes</li><li>Victoria (État)</li></region><settlement><li>Grenoble</li><li>Melbourne</li><li>University Park (Pennsylvanie)</li></settlement><orgName><li>Université Grenoble-Alpes</li><li>Université d'État de Pennsylvanie</li><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><region name="Victoria (État)"><name sortKey="Shears, Melanie J" sort="Shears, Melanie J" uniqKey="Shears M" first="Melanie J" last="Shears">Melanie J. Shears</name></region><name sortKey="Goodman, Christopher D" sort="Goodman, Christopher D" uniqKey="Goodman C" first="Christopher D" last="Goodman">Christopher D. Goodman</name><name sortKey="Mcconville, Malcolm J" sort="Mcconville, Malcolm J" uniqKey="Mcconville M" first="Malcolm J" last="Mcconville">Malcolm J. Mcconville</name><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I" last="Mcfadden">Geoffrey I. Mcfadden</name><name sortKey="Mollard, Vanessa" sort="Mollard, Vanessa" uniqKey="Mollard V" first="Vanessa" last="Mollard">Vanessa Mollard</name><name sortKey="Sturm, Angelika" sort="Sturm, Angelika" uniqKey="Sturm A" first="Angelika" last="Sturm">Angelika Sturm</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Macrae, James I" sort="Macrae, James I" uniqKey="Macrae J" first="James I" last="Macrae">James I. Macrae</name></noRegion></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Orchard, Lindsey M" sort="Orchard, Lindsey M" uniqKey="Orchard L" first="Lindsey M" last="Orchard">Lindsey M. Orchard</name></region><name sortKey="Llinas, Manuel" sort="Llinas, Manuel" uniqKey="Llinas M" first="Manuel" last="Llinás">Manuel Llinás</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Botte, Cyrille Y" sort="Botte, Cyrille Y" uniqKey="Botte C" first="Cyrille Y" last="Botté">Cyrille Y. Botté</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.
}}
Pour générer des pages wiki
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| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |