Identification of Protein Interfaces between α-Synuclein, the Principal Component of Lewy Bodies in Parkinson Disease, and the Molecular Chaperones Human Hsc70 and the Yeast Ssa1p*
Identifieur interne : 000473 ( Pmc/Corpus ); précédent : 000472; suivant : 000474Identification of Protein Interfaces between α-Synuclein, the Principal Component of Lewy Bodies in Parkinson Disease, and the Molecular Chaperones Human Hsc70 and the Yeast Ssa1p*
Auteurs : Virginie Redeker ; Samantha Pemberton ; Willy Bienvenut ; Luc Bousset ; Ronald MelkiSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2012.
Abstract
Url:
DOI: 10.1074/jbc.M112.387530
PubMed: 22843682
PubMed Central: 3463349
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of Protein Interfaces between α-Synuclein, the Principal Component of Lewy Bodies in Parkinson Disease, and the Molecular Chaperones Human Hsc70 and the Yeast Ssa1p<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Redeker, Virginie" sort="Redeker, Virginie" uniqKey="Redeker V" first="Virginie" last="Redeker">Virginie Redeker</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Pemberton, Samantha" sort="Pemberton, Samantha" uniqKey="Pemberton S" first="Samantha" last="Pemberton">Samantha Pemberton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bienvenut, Willy" sort="Bienvenut, Willy" uniqKey="Bienvenut W" first="Willy" last="Bienvenut">Willy Bienvenut</name><affiliation><nlm:aff id="aff2">Centre de Recherche de Gif, FRC3115, CNRS, 91198 Gif-sur-Yvette, France</nlm:aff></affiliation></author><author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22843682</idno><idno type="pmc">3463349</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463349</idno><idno type="RBID">PMC:3463349</idno><idno type="doi">10.1074/jbc.M112.387530</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000473</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000473</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of Protein Interfaces between α-Synuclein, the Principal Component of Lewy Bodies in Parkinson Disease, and the Molecular Chaperones Human Hsc70 and the Yeast Ssa1p<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Redeker, Virginie" sort="Redeker, Virginie" uniqKey="Redeker V" first="Virginie" last="Redeker">Virginie Redeker</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Pemberton, Samantha" sort="Pemberton, Samantha" uniqKey="Pemberton S" first="Samantha" last="Pemberton">Samantha Pemberton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bienvenut, Willy" sort="Bienvenut, Willy" uniqKey="Bienvenut W" first="Willy" last="Bienvenut">Willy Bienvenut</name><affiliation><nlm:aff id="aff2">Centre de Recherche de Gif, FRC3115, CNRS, 91198 Gif-sur-Yvette, France</nlm:aff></affiliation></author><author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><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="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> The mechanism by which molecular chaperones sequester α-synuclein is unknown.</p><p><bold>Results:</bold> We identify the surface interfaces involved in Hsc70 and Ssa1p interaction with α-synuclein.</p><p><bold>Conclusion:</bold> Hsc70 and Ssa1p bind α-synuclein like a tweezer through the two tips of their client protein binding sites.</p><p><bold>Significance:</bold> Elucidating how molecular chaperones bind proteins involved in neurodegenerative diseases is relevant to design 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">22843682</article-id><article-id pub-id-type="pmc">3463349</article-id><article-id pub-id-type="publisher-id">M112.387530</article-id><article-id pub-id-type="doi">10.1074/jbc.M112.387530</article-id><article-categories><subj-group subj-group-type="heading"><subject>Molecular Bases of Disease</subject></subj-group></article-categories><title-group><article-title>Identification of Protein Interfaces between α-Synuclein, the Principal Component of Lewy Bodies in Parkinson Disease, and the Molecular Chaperones Human Hsc70 and the Yeast Ssa1p<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">Hsc70- and Ssa1p-α-Synuclein Interaction Interfaces</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Redeker</surname><given-names>Virginie</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pemberton</surname><given-names>Samantha</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bienvenut</surname><given-names>Willy</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bousset</surname><given-names>Luc</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Melki</surname><given-names>Ronald</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 91198 Gif-sur-Yvette, France and</aff><aff id="aff2"><label>§</label>Centre de Recherche de Gif, FRC3115, CNRS, 91198 Gif-sur-Yvette, France</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed: <addr-line>Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.</addr-line> Tel.: <phone>33-16-982-3503</phone>; Fax: <fax>33-16-982-3129</fax>; E-mail: <email>melki@lebs.cnrs-gif.fr</email>.</corresp><fn fn-type="equal" id="FN2"><label>1</label><p>Both authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>21</day><month>9</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>26</day><month>7</month><year>2012</year></pub-date><volume>287</volume><issue>39</issue><fpage>32630</fpage><lpage>32639</lpage><history><date date-type="received"><day>5</day><month>6</month><year>2012</year></date><date date-type="rev-recd"><day>24</day><month>7</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2012</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc03912032630.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> The mechanism by which molecular chaperones sequester α-synuclein is unknown.</p><p><bold>Results:</bold> We identify the surface interfaces involved in Hsc70 and Ssa1p interaction with α-synuclein.</p><p><bold>Conclusion:</bold> Hsc70 and Ssa1p bind α-synuclein like a tweezer through the two tips of their client protein binding sites.</p><p><bold>Significance:</bold> Elucidating how molecular chaperones bind proteins involved in neurodegenerative diseases is relevant to design therapeutic tools.</p></abstract><abstract><p>Fibrillar α-synuclein (α-Syn) is the principal component of Lewy bodies, which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn plays a central role in PD progression as it has been shown to propagate between neurons. Tools that interfere with α-Syn assembly or change the physicochemical properties of the fibrils have potential therapeutic properties as they may be sufficient to interfere with and/or halt cell-to-cell transmission and the systematic spread of α-Syn assemblies within the central nervous system. Vertebrate molecular chaperones from the constitutive/heat-inducible heat shock protein 70 (Hsc/p70) family have been shown to hinder the assembly of soluble α-Syn into fibrils and to bind to the fibrils and very significantly reduce their toxicity. To understand how Hsc70 family members sequester soluble α-Syn, we set up experiments to identify the molecular chaperone-α-Syn surface interfaces. We cross-linked human Hsc70 and its yeast homologue Ssa1p and α-Syn using a chemical cross-linker and mapped the Hsc70- and Ssa1p-α-Syn interface. We show that the client binding domain of Hsc70 and Ssa1p binds two regions within α-Syn similar to a tweezer, with the first spanning residues 10–45 and the second spanning residues 97–102. Our findings define what is necessary and sufficient for engineering Hsc70- and Ssa1p-derived polypeptide with minichaperone properties with a potential as therapeutic agents in Parkinson disease through their ability to affect α-Syn assembly and/or toxicity.</p></abstract><kwd-group><kwd>Mass Spectrometry (MS)</kwd><kwd>Molecular Chaperone</kwd><kwd>Parkinson Disease</kwd><kwd>Protein Cross-linking</kwd><kwd>Protein-Protein Interactions</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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