ParkinsonFranceV1, Ncbi, Merge, bibRecord, 001601

Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation*

Identifieur interne : 001601 ( Ncbi/Merge ); précédent : 001600; suivant : 001602

Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation*

Auteurs : Elodie Monsellier [France] ; Virginie Redeker [France] ; Gemma Ruiz-Arlandis [France] ; Luc Bousset [France] ; Ronald Melki [France]

Source :

The Journal of Biological Chemistry [ 0021-9258 ] ; 2014.

RBID : PMC:4317008

Abstract

Background: Hsc70 has an alleviating effect on the toxicity of polyglutamine (polyQ)-containing proteins in vivo.

Results: Hsc70 binds specifically the N-terminal flank of huntingtin exon 1.

Conclusion: Hsc70 interaction with huntingtin exon 1 N-terminal flank affects the conformation of the resulting assemblies.

Significance: We identify the surface interfaces between Hsc70 and huntingtin exon 1, which allows the design of future therapeutic tools.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317008

DOI: 10.1074/jbc.M114.603332
PubMed: 25505179
PubMed Central: 4317008

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Le document en format XML

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<author><name sortKey="Monsellier, Elodie" sort="Monsellier, Elodie" uniqKey="Monsellier E" first="Elodie" last="Monsellier">Elodie Monsellier</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
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<author><name sortKey="Redeker, Virginie" sort="Redeker, Virginie" uniqKey="Redeker V" first="Virginie" last="Redeker">Virginie Redeker</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
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<author><name sortKey="Ruiz Arlandis, Gemma" sort="Ruiz Arlandis, Gemma" uniqKey="Ruiz Arlandis G" first="Gemma" last="Ruiz-Arlandis">Gemma Ruiz-Arlandis</name>
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<author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name>
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<author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation<xref ref-type="fn" rid="FN1">*</xref>
</title>
<author><name sortKey="Monsellier, Elodie" sort="Monsellier, Elodie" uniqKey="Monsellier E" first="Elodie" last="Monsellier">Elodie Monsellier</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Gif-sur-Yvette</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Redeker, Virginie" sort="Redeker, Virginie" uniqKey="Redeker V" first="Virginie" last="Redeker">Virginie Redeker</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Gif-sur-Yvette</settlement>
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</affiliation>
</author>
<author><name sortKey="Ruiz Arlandis, Gemma" sort="Ruiz Arlandis, Gemma" uniqKey="Ruiz Arlandis G" first="Gemma" last="Ruiz-Arlandis">Gemma Ruiz-Arlandis</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Gif-sur-Yvette</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Gif-sur-Yvette</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Gif-sur-Yvette</settlement>
</placeName>
</affiliation>
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<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p><bold>Background:</bold>
 Hsc70 has an alleviating effect on the toxicity of polyglutamine (polyQ)-containing proteins <italic>in vivo</italic>
.</p>
<p><bold>Results:</bold>
 Hsc70 binds specifically the N-terminal flank of huntingtin exon 1.</p>
<p><bold>Conclusion:</bold>
 Hsc70 interaction with huntingtin exon 1 N-terminal flank affects the conformation of the resulting assemblies.</p>
<p><bold>Significance:</bold>
 We identify the surface interfaces between Hsc70 and huntingtin exon 1, which allows the design of future therapeutic tools.</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">J Biol Chem</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id>
<journal-id journal-id-type="hwp">jbc</journal-id>
<journal-id journal-id-type="pmc">jbc</journal-id>
<journal-id journal-id-type="publisher-id">JBC</journal-id>
<journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9258</issn>
<issn pub-type="epub">1083-351X</issn>
<publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name>
<publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25505179</article-id>
<article-id pub-id-type="pmc">4317008</article-id>
<article-id pub-id-type="publisher-id">M114.603332</article-id>
<article-id pub-id-type="doi">10.1074/jbc.M114.603332</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Molecular Bases of Disease</subject>
</subj-group>
</article-categories>
<title-group><article-title>Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation<xref ref-type="fn" rid="FN1">*</xref>
</article-title>
<alt-title alt-title-type="short">Molecular Interaction between Hsc70 and Huntingtin Exon 1</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Monsellier</surname>
<given-names>Elodie</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
<xref ref-type="corresp" rid="cor1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Redeker</surname>
<given-names>Virginie</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ruiz-Arlandis</surname>
<given-names>Gemma</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bousset</surname>
<given-names>Luc</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Melki</surname>
<given-names>Ronald</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
<xref ref-type="corresp" rid="cor2"><sup>2</sup>
</xref>
</contrib>
<aff id="aff1">From the Neuroscience Paris-Saclay Institute, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>1</label>
 To whom correspondence may be addressed. Tel.: <phone>33-16982-3486</phone>
; E-mail: <email>monsellier@lebs.cnrs-gif.fr</email>
.</corresp>
<corresp id="cor2"><label>2</label>
 To whom correspondence may be addressed. Tel.: <phone>33-16982-3503</phone>
; E-mail: <email>melki@lebs.cnrs-gif.fr</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><day>30</day>
<month>1</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>10</day>
<month>12</month>
<year>2014</year>
</pub-date>
<volume>290</volume>
<issue>5</issue>
<fpage>2560</fpage>
<lpage>2576</lpage>
<history><date date-type="received"><day>26</day>
<month>8</month>
<year>2014</year>
</date>
<date date-type="rev-recd"><day>18</day>
<month>11</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement>
<copyright-year>2015</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc00515002560.pdf"></self-uri>
<abstract abstract-type="teaser"><p><bold>Background:</bold>
 Hsc70 has an alleviating effect on the toxicity of polyglutamine (polyQ)-containing proteins <italic>in vivo</italic>
.</p>
<p><bold>Results:</bold>
 Hsc70 binds specifically the N-terminal flank of huntingtin exon 1.</p>
<p><bold>Conclusion:</bold>
 Hsc70 interaction with huntingtin exon 1 N-terminal flank affects the conformation of the resulting assemblies.</p>
<p><bold>Significance:</bold>
 We identify the surface interfaces between Hsc70 and huntingtin exon 1, which allows the design of future therapeutic tools.</p>
</abstract>
<abstract><p>The aggregation of polyglutamine (polyQ)-containing proteins is at the origin of nine neurodegenerative diseases. Molecular chaperones prevent the aggregation of polyQ-containing proteins. The exact mechanism by which they interact with polyQ-containing, aggregation-prone proteins and interfere with their assembly is unknown. Here we dissect the mechanism of interaction between a huntingtin exon 1 fragment of increasing polyQ lengths (HttEx1Qn), the aggregation of which is tightly associated with Huntington's disease, and molecular chaperone Hsc70. We show that Hsc70, together with its Hsp40 co-chaperones, inhibits HttEx1Qn aggregation and modifies the structural, seeding, and infectious properties of the resulting fibrils in a polyQ-independent manner. We demonstrate that Hsc70 binds the 17-residue-long N-terminal flank of HttEx1Qn, and we map Hsc70-HttEx1Qn surface interfaces at the residue level. Finally, we show that this interaction competes with homotypic interactions between the N termini of different HttEx1Qn molecules that trigger the aggregation process. Our results lay the foundations of future therapeutic strategies targeting huntingtin aggregation in Huntington disease.</p>
</abstract>
<kwd-group><kwd>Heat Shock Protein (HSP)</kwd>
<kwd>Huntington Disease</kwd>
<kwd>Mass Spectrometry (MS)</kwd>
<kwd>Molecular Chaperone</kwd>
<kwd>Neurodegenerative Disease</kwd>
<kwd>Polyglutamine</kwd>
<kwd>Protein Aggregation</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>France</li>
</country>
<region><li>Île-de-France</li>
</region>
<settlement><li>Gif-sur-Yvette</li>
</settlement>
</list>
<tree><country name="France"><region name="Île-de-France"><name sortKey="Monsellier, Elodie" sort="Monsellier, Elodie" uniqKey="Monsellier E" first="Elodie" last="Monsellier">Elodie Monsellier</name>
</region>
<name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name>
<name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name>
<name sortKey="Redeker, Virginie" sort="Redeker, Virginie" uniqKey="Redeker V" first="Virginie" last="Redeker">Virginie Redeker</name>
<name sortKey="Ruiz Arlandis, Gemma" sort="Ruiz Arlandis, Gemma" uniqKey="Ruiz Arlandis G" first="Gemma" last="Ruiz-Arlandis">Gemma Ruiz-Arlandis</name>
</country>
</tree>
</affiliations>
</record>

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	La maladie de Parkinson en France (serveur d'exploration)
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Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation*

Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation*

Source :

Abstract

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

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki