RapamycinFungusV1, Main, Exploration, bibRecord, 000729

TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.

Identifieur interne : 000729 ( Main/Exploration ); précédent : 000728; suivant : 000730

TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.

Auteurs : Manoël Prouteau [Suisse] ; Ambroise Desfosses [Nouvelle-Zélande] ; Christian Sieben [Suisse] ; Clélia Bourgoint [Suisse] ; Nour Lydia Mozaffari [Suisse] ; Davide Demurtas [Suisse] ; Alok K. Mitra [Nouvelle-Zélande] ; Paul Guichard [Suisse] ; Suliana Manley [Suisse] ; Robbie Loewith [Suisse]

Source :

Nature [ 1476-4687 ] ; 2017.

RBID : pubmed:28976958

Descripteurs français

KwdFr :
- Activation enzymatique (MeSH), Allèles (MeSH), Complexe-1 cible mécanistique de la rapamycine (composition chimique), Complexe-1 cible mécanistique de la rapamycine (métabolisme), Complexe-1 cible mécanistique de la rapamycine (ultrastructure), Cryomicroscopie électronique (MeSH), Domaine catalytique (MeSH), Glucose (déficit), Glucose (métabolisme), Glucose (pharmacologie), Protéines G monomériques (déficit), Protéines G monomériques (génétique), Protéines de Saccharomyces cerevisiae (génétique), Saccharomyces cerevisiae (effets des médicaments et des substances chimiques), Saccharomyces cerevisiae (enzymologie), Saccharomyces cerevisiae (génétique), Saccharomyces cerevisiae (ultrastructure).
MESH :
- composition chimique : Complexe-1 cible mécanistique de la rapamycine.
- déficit : Glucose, Protéines G monomériques.
- effets des médicaments et des substances chimiques : Saccharomyces cerevisiae.
- enzymologie : Saccharomyces cerevisiae.
- génétique : Protéines G monomériques, Protéines de Saccharomyces cerevisiae, Saccharomyces cerevisiae.
- métabolisme : Complexe-1 cible mécanistique de la rapamycine, Glucose.
- pharmacologie : Glucose.
- ultrastructure : Activation enzymatique, Allèles, Complexe-1 cible mécanistique de la rapamycine, Cryomicroscopie électronique, Domaine catalytique, Saccharomyces cerevisiae.

English descriptors

KwdEn :
- Alleles (MeSH), Catalytic Domain (MeSH), Cryoelectron Microscopy (MeSH), Enzyme Activation (MeSH), Glucose (deficiency), Glucose (metabolism), Glucose (pharmacology), Mechanistic Target of Rapamycin Complex 1 (chemistry), Mechanistic Target of Rapamycin Complex 1 (metabolism), Mechanistic Target of Rapamycin Complex 1 (ultrastructure), Monomeric GTP-Binding Proteins (deficiency), Monomeric GTP-Binding Proteins (genetics), Saccharomyces cerevisiae (drug effects), Saccharomyces cerevisiae (enzymology), Saccharomyces cerevisiae (genetics), Saccharomyces cerevisiae (ultrastructure), Saccharomyces cerevisiae Proteins (genetics).
MESH :
- chemical , chemistry : Mechanistic Target of Rapamycin Complex 1.
- chemical , deficiency : Glucose, Monomeric GTP-Binding Proteins.
- chemical , genetics : Monomeric GTP-Binding Proteins, Saccharomyces cerevisiae Proteins.
- chemical , metabolism : Glucose, Mechanistic Target of Rapamycin Complex 1.
- chemical , pharmacology : Glucose.
- chemical , ultrastructure : Mechanistic Target of Rapamycin Complex 1.
- drug effects : Saccharomyces cerevisiae.
- enzymology : Saccharomyces cerevisiae.
- genetics : Saccharomyces cerevisiae.
- ultrastructure : Saccharomyces cerevisiae.
- Alleles, Catalytic Domain, Cryoelectron Microscopy, Enzyme Activation.

Abstract

The target of rapamycin (TOR) is a eukaryotic serine/threonine protein kinase that functions in two distinct complexes, TORC1 and TORC2, to regulate growth and metabolism. GTPases, responding to signals generated by abiotic stressors, nutrients, and, in metazoans, growth factors, play an important but poorly understood role in TORC1 regulation. Here we report that, in budding yeast, glucose withdrawal (which leads to an acute loss of TORC1 kinase activity) triggers a similarly rapid Rag GTPase-dependent redistribution of TORC1 from being semi-uniform around the vacuolar membrane to a single, vacuole-associated cylindrical structure visible by super-resolution optical microscopy. Three-dimensional reconstructions of cryo-electron micrograph images of these purified cylinders demonstrate that TORC1 oligomerizes into a higher-level hollow helical assembly, which we name a TOROID (TORC1 organized in inhibited domain). Fitting of the recently described mammalian TORC1 structure into our helical map reveals that oligomerization leads to steric occlusion of the active site. Guided by the implications from our reconstruction, we present a TOR1 allele that prevents both TOROID formation and TORC1 inactivation in response to glucose withdrawal, demonstrating that oligomerization is necessary for TORC1 inactivation. Our results reveal a novel mechanism by which Rag GTPases regulate TORC1 activity and suggest that the reversible assembly and/or disassembly of higher-level structures may be an underappreciated mechanism for the regulation of protein kinases.

DOI: 10.1038/nature24021
PubMed: 28976958
PubMed Central: PMC5640987

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.</title>
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<author><name sortKey="Lydia Mozaffari, Nour" sort="Lydia Mozaffari, Nour" uniqKey="Lydia Mozaffari N" first="Nour" last="Lydia Mozaffari">Nour Lydia Mozaffari</name>
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<affiliation wicri:level="4"><nlm:affiliation>Swiss National Centre for Competence in Research (NCCR) in Chemical Biology. University of Geneva, Sciences II, room 3-308, 30 Quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Swiss National Centre for Competence in Research (NCCR) in Chemical Biology. University of Geneva, Sciences II, room 3-308, 30 Quai Ernest-Ansermet, CH1211 Geneva</wicri:regionArea>
<orgName type="university">Université de Genève</orgName>
<placeName><settlement type="city">Genève</settlement>
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<author><name sortKey="Demurtas, Davide" sort="Demurtas, Davide" uniqKey="Demurtas D" first="Davide" last="Demurtas">Davide Demurtas</name>
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<affiliation wicri:level="1"><nlm:affiliation>School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.</nlm:affiliation>
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<author><name sortKey="Guichard, Paul" sort="Guichard, Paul" uniqKey="Guichard P" first="Paul" last="Guichard">Paul Guichard</name>
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<author><name sortKey="Manley, Suliana" sort="Manley, Suliana" uniqKey="Manley S" first="Suliana" last="Manley">Suliana Manley</name>
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<country xml:lang="fr">Suisse</country>
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<series><title level="j">Nature</title>
<idno type="eISSN">1476-4687</idno>
<imprint><date when="2017" type="published">2017</date>
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<term>Catalytic Domain (MeSH)</term>
<term>Cryoelectron Microscopy (MeSH)</term>
<term>Enzyme Activation (MeSH)</term>
<term>Glucose (deficiency)</term>
<term>Glucose (metabolism)</term>
<term>Glucose (pharmacology)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (chemistry)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (ultrastructure)</term>
<term>Monomeric GTP-Binding Proteins (deficiency)</term>
<term>Monomeric GTP-Binding Proteins (genetics)</term>
<term>Saccharomyces cerevisiae (drug effects)</term>
<term>Saccharomyces cerevisiae (enzymology)</term>
<term>Saccharomyces cerevisiae (genetics)</term>
<term>Saccharomyces cerevisiae (ultrastructure)</term>
<term>Saccharomyces cerevisiae Proteins (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation enzymatique (MeSH)</term>
<term>Allèles (MeSH)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (composition chimique)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (ultrastructure)</term>
<term>Cryomicroscopie électronique (MeSH)</term>
<term>Domaine catalytique (MeSH)</term>
<term>Glucose (déficit)</term>
<term>Glucose (métabolisme)</term>
<term>Glucose (pharmacologie)</term>
<term>Protéines G monomériques (déficit)</term>
<term>Protéines G monomériques (génétique)</term>
<term>Protéines de Saccharomyces cerevisiae (génétique)</term>
<term>Saccharomyces cerevisiae (effets des médicaments et des substances chimiques)</term>
<term>Saccharomyces cerevisiae (enzymologie)</term>
<term>Saccharomyces cerevisiae (génétique)</term>
<term>Saccharomyces cerevisiae (ultrastructure)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Glucose</term>
<term>Monomeric GTP-Binding Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Monomeric GTP-Binding Proteins</term>
<term>Saccharomyces cerevisiae Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Glucose</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="ultrastructure" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Glucose</term>
<term>Protéines G monomériques</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines G monomériques</term>
<term>Protéines de Saccharomyces cerevisiae</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Glucose</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Glucose</term>
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<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Saccharomyces cerevisiae</term>
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<term>Cryoelectron Microscopy</term>
<term>Enzyme Activation</term>
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<term>Allèles</term>
<term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Cryomicroscopie électronique</term>
<term>Domaine catalytique</term>
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<front><div type="abstract" xml:lang="en">The target of rapamycin (TOR) is a eukaryotic serine/threonine protein kinase that functions in two distinct complexes, TORC1 and TORC2, to regulate growth and metabolism. GTPases, responding to signals generated by abiotic stressors, nutrients, and, in metazoans, growth factors, play an important but poorly understood role in TORC1 regulation. Here we report that, in budding yeast, glucose withdrawal (which leads to an acute loss of TORC1 kinase activity) triggers a similarly rapid Rag GTPase-dependent redistribution of TORC1 from being semi-uniform around the vacuolar membrane to a single, vacuole-associated cylindrical structure visible by super-resolution optical microscopy. Three-dimensional reconstructions of cryo-electron micrograph images of these purified cylinders demonstrate that TORC1 oligomerizes into a higher-level hollow helical assembly, which we name a TOROID (TORC1 organized in inhibited domain). Fitting of the recently described mammalian TORC1 structure into our helical map reveals that oligomerization leads to steric occlusion of the active site. Guided by the implications from our reconstruction, we present a TOR1 allele that prevents both TOROID formation and TORC1 inactivation in response to glucose withdrawal, demonstrating that oligomerization is necessary for TORC1 inactivation. Our results reveal a novel mechanism by which Rag GTPases regulate TORC1 activity and suggest that the reversible assembly and/or disassembly of higher-level structures may be an underappreciated mechanism for the regulation of protein kinases.</div>
</front>
</TEI>
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<DateCompleted><Year>2018</Year>
<Month>02</Month>
<Day>27</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-4687</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>550</Volume>
<Issue>7675</Issue>
<PubDate><Year>2017</Year>
<Month>10</Month>
<Day>12</Day>
</PubDate>
</JournalIssue>
<Title>Nature</Title>
<ISOAbbreviation>Nature</ISOAbbreviation>
</Journal>
<ArticleTitle>TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.</ArticleTitle>
<Pagination><MedlinePgn>265-269</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/nature24021</ELocationID>
<Abstract><AbstractText>The target of rapamycin (TOR) is a eukaryotic serine/threonine protein kinase that functions in two distinct complexes, TORC1 and TORC2, to regulate growth and metabolism. GTPases, responding to signals generated by abiotic stressors, nutrients, and, in metazoans, growth factors, play an important but poorly understood role in TORC1 regulation. Here we report that, in budding yeast, glucose withdrawal (which leads to an acute loss of TORC1 kinase activity) triggers a similarly rapid Rag GTPase-dependent redistribution of TORC1 from being semi-uniform around the vacuolar membrane to a single, vacuole-associated cylindrical structure visible by super-resolution optical microscopy. Three-dimensional reconstructions of cryo-electron micrograph images of these purified cylinders demonstrate that TORC1 oligomerizes into a higher-level hollow helical assembly, which we name a TOROID (TORC1 organized in inhibited domain). Fitting of the recently described mammalian TORC1 structure into our helical map reveals that oligomerization leads to steric occlusion of the active site. Guided by the implications from our reconstruction, we present a TOR1 allele that prevents both TOROID formation and TORC1 inactivation in response to glucose withdrawal, demonstrating that oligomerization is necessary for TORC1 inactivation. Our results reveal a novel mechanism by which Rag GTPases regulate TORC1 activity and suggest that the reversible assembly and/or disassembly of higher-level structures may be an underappreciated mechanism for the regulation of protein kinases.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Prouteau</LastName>
<ForeName>Manoël</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Desfosses</LastName>
<ForeName>Ambroise</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sieben</LastName>
<ForeName>Christian</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Institute of Physics, Laboratory of Experimental Biophysics, École Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Swiss National Centre for Competence in Research (NCCR) in Chemical Biology. University of Geneva, Sciences II, room 3-308, 30 Quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bourgoint</LastName>
<ForeName>Clélia</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lydia Mozaffari</LastName>
<ForeName>Nour</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Physics, Laboratory of Experimental Biophysics, École Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Swiss National Centre for Competence in Research (NCCR) in Chemical Biology. University of Geneva, Sciences II, room 3-308, 30 Quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Demurtas</LastName>
<ForeName>Davide</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Interdisciplinary Centre for Electron Microscopy, École Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mitra</LastName>
<ForeName>Alok K</ForeName>
<Initials>AK</Initials>
<AffiliationInfo><Affiliation>School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Guichard</LastName>
<ForeName>Paul</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Manley</LastName>
<ForeName>Suliana</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Institute of Physics, Laboratory of Experimental Biophysics, École Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Swiss National Centre for Competence in Research (NCCR) in Chemical Biology. University of Geneva, Sciences II, room 3-308, 30 Quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Loewith</LastName>
<ForeName>Robbie</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Biology, University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, 30 quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Swiss National Centre for Competence in Research (NCCR) in Chemical Biology. University of Geneva, Sciences II, room 3-308, 30 Quai Ernest-Ansermet, CH1211 Geneva, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>243016</GrantID>
<Agency>European Research Council</Agency>
<Country>International</Country>
</Grant>
<Grant><GrantID>614552</GrantID>
<Agency>European Research Council</Agency>
<Country>International</Country>
</Grant>
</GrantList>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>10</Month>
<Day>04</Day>
</ArticleDate>
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<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Nature</MedlineTA>
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<ISSNLinking>0028-0836</ISSNLinking>
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<NameOfSubstance UI="C121263">GTR2 protein, S cerevisiae</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C121262">Gtr1 protein, S cerevisiae</NameOfSubstance>
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<MeshHeading><DescriptorName UI="D012441" MajorTopicYN="N">Saccharomyces cerevisiae</DescriptorName>
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<Month>08</Month>
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<ReferenceList><Reference><Citation>Nat Protoc. 2015 Jul;10(7):1007-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26068895</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2013 Jul 17;8(7):e69004</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23874848</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Struct Biol. 2003 Jun;142(3):334-47</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12781660</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2015 Jun 12;290(24):14963-78</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25882841</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2002 Oct;58(Pt 10 Pt 2):1820-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12351826</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Methods. 2013 Jul;10(7):653-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23708387</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Chem Biol. 2016 Jun 17;11(6):1511-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26999075</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cell. 2015 Jun 18;58(6):977-88</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26028537</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Methods Enzymol. 2010;482:167-83</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20888961</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Commun. 2016 Apr 13;7:11016</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27072897</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Elife. 2015 Oct 06;4:null</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26439012</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Cell Sci. 2012 Apr 15;125(Pt 8):1920-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22344254</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Photonics. 2016 Nov;10 (11):705-708</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27818707</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Bioinformatics. 2014 Aug 15;30(16):2389-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24771516</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Elife. 2014 Apr 25;:null</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24771766</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2015 Jan 9;347(6218):194-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25567907</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Comput Chem. 2004 Oct;25(13):1605-12</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15264254</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cell. 2009 Sep 11;35(5):563-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19748353</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Struct Biol. 2014 Jan;185(1):15-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24269218</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Trends Cell Biol. 2016 Feb;26(2):148-159</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26546292</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Eukaryot Cell. 2008 Oct;7(10):1819-30</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18723607</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2016 Jan 1;351(6268):48-52</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26678875</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cell. 2007 Jun 8;26(5):663-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17560372</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Res. 2015 Sep;25(9):1043-59</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26206314</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biophys J. 2006 Dec 1;91(11):4258-72</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16980368</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Biol Cell. 2016 Jan 15;27(2):382-96</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26609069</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2006 Feb 10;124(3):471-84</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16469695</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Arch Biochem Biophys. 2015 Sep 1;581:54-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25912526</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Methods. 2006 Nov;3(11):887-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17060912</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Sci Signal. 2013 May 28;6(277):ra42</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23716719</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Struct Biol. 2007 Jan;157(1):38-46</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16859925</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cell. 2002 Sep;10(3):457-68</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12408816</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Methods. 2006 Oct;3(10):793-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16896339</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Methods. 2012 Jun;9(6):582-4</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22543348</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2017 Mar 9;168(6):960-976</Citation>
<ArticleIdList><ArticleId IdType="pubmed">28283069</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Curr Protoc Mol Biol. 2010 Oct;Chapter 14:Unit14.20</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20890901</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2004 Apr 9;279(15):14752-62</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14736892</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nature. 2013 May 9;497(7448):217-23</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23636326</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Methods Cell Biol. 2015;129:191-209</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26175440</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2006 Sep 15;313(5793):1642-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16902090</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
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<name sortKey="Loewith, Robbie" sort="Loewith, Robbie" uniqKey="Loewith R" first="Robbie" last="Loewith">Robbie Loewith</name>
<name sortKey="Loewith, Robbie" sort="Loewith, Robbie" uniqKey="Loewith R" first="Robbie" last="Loewith">Robbie Loewith</name>
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	Serveur d'exploration sur la rapamycine et les champignons
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Serveur d'exploration sur la rapamycine et les champignons

TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.

TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity.

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