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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ligand-binding properties of a juvenile hormone receptor, Methoprene-tolerant</title><author><name sortKey="Charles, Jean Philippe" sort="Charles, Jean Philippe" uniqKey="Charles J" first="Jean-Philippe" last="Charles">Jean-Philippe Charles</name><affiliation><nlm:aff id="aff1">Centre des Sciences du Gout et de l'Alimentation, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6265, Institut National de la Recherche Agronomique Unité Mixte de Recherche 1324,<institution>Université de Bourgogne</institution>, 21000 Dijon,<country>France</country>;</nlm:aff></affiliation></author><author><name sortKey="Iwema, Thomas" sort="Iwema, Thomas" uniqKey="Iwema T" first="Thomas" last="Iwema">Thomas Iwema</name><affiliation><nlm:aff id="aff2">Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5075,<institution>Université Joseph Fourier Grenoble 1</institution>, 38027 Grenoble,<country>France</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Groupe de Recherche Immunopathologies et Maladies Infectieuses, University of La Réunion,<institution>Cyclotron Réunion Océan Indien</institution>, 97491 Ste Clotilde, Réunion,<country>France</country>;</nlm:aff></affiliation></author><author><name sortKey="Epa, V Chandana" sort="Epa, V Chandana" uniqKey="Epa V" first="V. Chandana" last="Epa">V. Chandana Epa</name><affiliation><nlm:aff id="aff4">Division of Materials Science and Engineering,<institution>Commonwealth Scientific and Industrial Research Organization</institution>, Parkville, Victoria 3052,<country>Australia</country>;</nlm:aff></affiliation></author><author><name sortKey="Takaki, Keiko" sort="Takaki, Keiko" uniqKey="Takaki K" first="Keiko" last="Takaki">Keiko Takaki</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Biology Center,<institution>Academy of Sciences of the Czech Republic</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></nlm:aff></affiliation></author><author><name sortKey="Rynes, Jan" sort="Rynes, Jan" uniqKey="Rynes J" first="Jan" last="Rynes">Jan Rynes</name><affiliation><nlm:aff id="aff6">Department of Molecular Biology,<institution>University of South Bohemia</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></nlm:aff></affiliation></author><author><name sortKey="Jindra, Marek" sort="Jindra, Marek" uniqKey="Jindra M" first="Marek" last="Jindra">Marek Jindra</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Biology Center,<institution>Academy of Sciences of the Czech Republic</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22167806</idno><idno type="pmc">3248530</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248530</idno><idno type="RBID">PMC:3248530</idno><idno type="doi">10.1073/pnas.1116123109</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001B54</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B54</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ligand-binding properties of a juvenile hormone receptor, Methoprene-tolerant</title><author><name sortKey="Charles, Jean Philippe" sort="Charles, Jean Philippe" uniqKey="Charles J" first="Jean-Philippe" last="Charles">Jean-Philippe Charles</name><affiliation><nlm:aff id="aff1">Centre des Sciences du Gout et de l'Alimentation, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6265, Institut National de la Recherche Agronomique Unité Mixte de Recherche 1324,<institution>Université de Bourgogne</institution>, 21000 Dijon,<country>France</country>;</nlm:aff></affiliation></author><author><name sortKey="Iwema, Thomas" sort="Iwema, Thomas" uniqKey="Iwema T" first="Thomas" last="Iwema">Thomas Iwema</name><affiliation><nlm:aff id="aff2">Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5075,<institution>Université Joseph Fourier Grenoble 1</institution>, 38027 Grenoble,<country>France</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Groupe de Recherche Immunopathologies et Maladies Infectieuses, University of La Réunion,<institution>Cyclotron Réunion Océan Indien</institution>, 97491 Ste Clotilde, Réunion,<country>France</country>;</nlm:aff></affiliation></author><author><name sortKey="Epa, V Chandana" sort="Epa, V Chandana" uniqKey="Epa V" first="V. Chandana" last="Epa">V. Chandana Epa</name><affiliation><nlm:aff id="aff4">Division of Materials Science and Engineering,<institution>Commonwealth Scientific and Industrial Research Organization</institution>, Parkville, Victoria 3052,<country>Australia</country>;</nlm:aff></affiliation></author><author><name sortKey="Takaki, Keiko" sort="Takaki, Keiko" uniqKey="Takaki K" first="Keiko" last="Takaki">Keiko Takaki</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Biology Center,<institution>Academy of Sciences of the Czech Republic</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></nlm:aff></affiliation></author><author><name sortKey="Rynes, Jan" sort="Rynes, Jan" uniqKey="Rynes J" first="Jan" last="Rynes">Jan Rynes</name><affiliation><nlm:aff id="aff6">Department of Molecular Biology,<institution>University of South Bohemia</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></nlm:aff></affiliation></author><author><name sortKey="Jindra, Marek" sort="Jindra, Marek" uniqKey="Jindra M" first="Marek" last="Jindra">Marek Jindra</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Biology Center,<institution>Academy of Sciences of the Czech Republic</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Juvenile hormone (JH) is a sesquiterpenoid of vital importance for insect development, yet the molecular basis of JH signaling remains obscure, mainly because a bona fide JH receptor has not been identified. Mounting evidence points to the basic helix–loop–helix (bHLH)/Per-Arnt-Sim (PAS) domain protein Methoprene-tolerant (Met) as the best JH receptor candidate. However, details of how Met transduces the hormonal signal are missing. Here, we demonstrate that Met specifically binds JH III and its biologically active mimics, methoprene and pyriproxyfen, through its C-terminal PAS domain. Substitution of individual amino acids, predicted to form a ligand-binding pocket, with residues possessing bulkier side chains reduces JH III binding likely because of steric hindrance. Although a mutation that abolishes JH III binding does not affect a Met–Met complex that forms in the absence of methoprene, it prevents both the ligand-dependent dissociation of the Met–Met dimer and the ligand-dependent interaction of Met with its partner bHLH-PAS protein Taiman. These results show that Met can sense the JH signal through direct, specific binding, thus establishing a unique class of intracellular hormone receptors.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22167806</article-id><article-id pub-id-type="pmc">3248530</article-id><article-id pub-id-type="publisher-id">201116123</article-id><article-id pub-id-type="doi">10.1073/pnas.1116123109</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Developmental Biology</subject></subj-group></subj-group></article-categories><title-group><article-title>Ligand-binding properties of a juvenile hormone receptor, Methoprene-tolerant</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Charles</surname><given-names>Jean-Philippe</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Iwema</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Epa</surname><given-names>V. Chandana</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Takaki</surname><given-names>Keiko</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rynes</surname><given-names>Jan</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jindra</surname><given-names>Marek</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>Centre des Sciences du Gout et de l'Alimentation, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6265, Institut National de la Recherche Agronomique Unité Mixte de Recherche 1324,<institution>Université de Bourgogne</institution>, 21000 Dijon,<country>France</country>;</aff><aff id="aff2"><sup>b</sup>Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5075,<institution>Université Joseph Fourier Grenoble 1</institution>, 38027 Grenoble,<country>France</country>;</aff><aff id="aff3"><sup>c</sup>Groupe de Recherche Immunopathologies et Maladies Infectieuses, University of La Réunion,<institution>Cyclotron Réunion Océan Indien</institution>, 97491 Ste Clotilde, Réunion,<country>France</country>;</aff><aff id="aff4"><sup>d</sup>Division of Materials Science and Engineering,<institution>Commonwealth Scientific and Industrial Research Organization</institution>, Parkville, Victoria 3052,<country>Australia</country>;</aff><aff id="aff5"><sup>e</sup>Biology Center,<institution>Academy of Sciences of the Czech Republic</institution>, Ceske Budejovice 37005,<country>Czech Republic</country>; and</aff><aff id="aff6"><sup>f</sup>Department of Molecular Biology,<institution>University of South Bohemia</institution>, Ceske Budejovice 37005,<country>Czech Republic</country></aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence should be addressed. E-mail: <email>jindra@entu.cas.cz</email>.</corresp><fn fn-type="edited-by"><p>Edited by Lynn M. Riddiford, Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA, and approved November 17, 2011 (received for review September 30, 2011)</p></fn><fn fn-type="con"><p>Author contributions: J.-P.C., T.I., and M.J. designed research; J.-P.C., T.I., V.C.E., K.T., J.R., and M.J. performed research; J.-P.C., T.I., and V.C.E. contributed new reagents/analytic tools; J.-P.C., T.I., V.C.E., and M.J. analyzed data; and M.J. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>27</day><month>12</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>13</day><month>12</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>13</day><month>12</month><year>2011</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>108</volume><issue>52</issue><fpage>21128</fpage><lpage>21133</lpage><permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201116123.pdf"></self-uri><abstract><p>Juvenile hormone (JH) is a sesquiterpenoid of vital importance for insect development, yet the molecular basis of JH signaling remains obscure, mainly because a bona fide JH receptor has not been identified. Mounting evidence points to the basic helix–loop–helix (bHLH)/Per-Arnt-Sim (PAS) domain protein Methoprene-tolerant (Met) as the best JH receptor candidate. However, details of how Met transduces the hormonal signal are missing. Here, we demonstrate that Met specifically binds JH III and its biologically active mimics, methoprene and pyriproxyfen, through its C-terminal PAS domain. Substitution of individual amino acids, predicted to form a ligand-binding pocket, with residues possessing bulkier side chains reduces JH III binding likely because of steric hindrance. Although a mutation that abolishes JH III binding does not affect a Met–Met complex that forms in the absence of methoprene, it prevents both the ligand-dependent dissociation of the Met–Met dimer and the ligand-dependent interaction of Met with its partner bHLH-PAS protein Taiman. These results show that Met can sense the JH signal through direct, specific binding, thus establishing a unique class of intracellular hormone receptors.</p></abstract><kwd-group><kwd>structure modeling</kwd><kwd>insecticide action</kwd><kwd>metamorphosis</kwd><kwd><italic>Tribolium</italic></kwd><kwd><italic>Drosophila</italic></kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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