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Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes

Identifieur interne : 000433 ( Ncbi/Merge ); précédent : 000432; suivant : 000434

Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes

Auteurs : R. A. Gangani D. Silva [États-Unis] ; Rong Huang [États-Unis] ; Jamie Morris [États-Unis] ; Jianwen Fang [États-Unis] ; Elena O. Gracheva [États-Unis] ; Gang Ren [États-Unis] ; Anatol Kontush [France] ; W. Gray Jerome [États-Unis] ; Kerry-Anne Rye [Australie] ; W. Sean Davidson [États-Unis]

Source :

RBID : PMC:2527885

Abstract

Spherical high density lipoproteins (HDL) predominate in human plasma. However, little information exists on the structure of the most common HDL protein, apolipoprotein (apo) A-I, in spheres vs. better studied discoidal forms. We produced spherical HDL by incubating reconstituted discoidal HDL with physiological plasma-remodeling enzymes and compared apoA-I structure in discs and spheres of comparable diameter (79–80 and 93–96 Å). Using cross-linking chemistry and mass spectrometry, we determined that the general structural organization of apoA-I was overall similar between discs and spheres, regardless of diameter. This was the case despite the fact that the 93 Å spheres contained three molecules of apoA-I per particle compared with only two in the discs. Thus, apoA-I adopts a consistent general structural framework in HDL particles—irrespective of shape, size and the number of apoA-Is present. Furthermore, a similar cross-linking pattern was demonstrated in HDL particles isolated from human serum. We propose the first experiment-based molecular model of apoA-I in spherical HDL particles. This model provides a new foundation for understanding how apoA-I structure modulates HDL function and metabolism.


Url:
DOI: 10.1073/pnas.0803626105
PubMed: 18719128
PubMed Central: 2527885

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PMC:2527885

Le document en format XML

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<orgName type="university">Université de Melbourne</orgName>
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<country xml:lang="fr">États-Unis</country>
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</placeName>
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<p>Spherical high density lipoproteins (HDL)
<sup></sup>
predominate in human plasma. However, little information exists on the structure of the most common HDL protein, apolipoprotein (apo) A-I, in spheres vs. better studied discoidal forms. We produced spherical HDL by incubating reconstituted discoidal HDL with physiological plasma-remodeling enzymes and compared apoA-I structure in discs and spheres of comparable diameter (79–80 and 93–96 Å). Using cross-linking chemistry and mass spectrometry, we determined that the general structural organization of apoA-I was overall similar between discs and spheres, regardless of diameter. This was the case despite the fact that the 93 Å spheres contained three molecules of apoA-I per particle compared with only two in the discs. Thus, apoA-I adopts a consistent general structural framework in HDL particles—irrespective of shape, size and the number of apoA-Is present. Furthermore, a similar cross-linking pattern was demonstrated in HDL particles isolated from human serum. We propose the first experiment-based molecular model of apoA-I in spherical HDL particles. This model provides a new foundation for understanding how apoA-I structure modulates HDL function and metabolism.</p>
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<article-id pub-id-type="pmc">2527885</article-id>
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<article-id pub-id-type="doi">10.1073/pnas.0803626105</article-id>
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<article-title>Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes</article-title>
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<contrib contrib-type="author">
<name>
<surname>Silva</surname>
<given-names>R. A. Gangani D.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>Rong</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Morris</surname>
<given-names>Jamie</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fang</surname>
<given-names>Jianwen</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gracheva</surname>
<given-names>Elena O.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ren</surname>
<given-names>Gang</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kontush</surname>
<given-names>Anatol</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>§</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jerome</surname>
<given-names>W. Gray</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rye</surname>
<given-names>Kerry-Anne</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup></sup>
</xref>
<xref ref-type="aff" rid="aff7">**</xref>
<xref ref-type="aff" rid="aff8">
<sup>††</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Davidson</surname>
<given-names>W. Sean</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
<xref ref-type="corresp" rid="cor1">
<sup>‡‡</sup>
</xref>
</contrib>
<aff id="aff1">*Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237;</aff>
<aff id="aff2">
<sup></sup>
Applied Bioinformatics Laboratory, University of Kansas, Lawrence, KS 66047;</aff>
<aff id="aff3">
<sup></sup>
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158;</aff>
<aff id="aff4">
<sup>§</sup>
Unité Mixte de Recherche S551, Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie and Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpétrière, F-75013 Paris, France;</aff>
<aff id="aff5">
<sup></sup>
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232;</aff>
<aff id="aff6">
<sup></sup>
Lipid Research Group, Heart Research Institute, Camperdown NSW 2050, Australia,</aff>
<aff id="aff7">**Faculty of Medicine, University of Sydney, NSW 2006, Australia; and</aff>
<aff id="aff8">
<sup>††</sup>
Department of Medicine, University of Melbourne, Vic 3010, Australia</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">
<sup>‡‡</sup>
To whom correspondence may be addressed. E-mail:
<email>sean.davidson@uc.edu</email>
</corresp>
<fn fn-type="edited-by">
<p>Edited by Richard J. Havel, University of California School of Medicine, San Francisco, CA, and approved June 21, 2008</p>
</fn>
<fn fn-type="con">
<p>Author contributions: R.A.G.D.S. and W.S.D. designed research; R.A.G.D.S., R.H., J.M., E.O.G., G.R., A.K., W.G.J., K.-A.R., and W.S.D. performed research; R.A.G.D.S., R.H., J.F., W.G.J., and W.S.D. analyzed data; and R.A.G.D.S. and W.S.D. wrote the paper.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<day>26</day>
<month>8</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub">
<day>21</day>
<month>8</month>
<year>2008</year>
</pub-date>
<volume>105</volume>
<issue>34</issue>
<fpage>12176</fpage>
<lpage>12181</lpage>
<history>
<date date-type="received">
<day>14</day>
<month>4</month>
<year>2008</year>
</date>
</history>
<permissions>
<copyright-statement>© 2008 by The National Academy of Sciences of the USA</copyright-statement>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq03408012176.pdf"></self-uri>
<abstract>
<p>Spherical high density lipoproteins (HDL)
<sup></sup>
predominate in human plasma. However, little information exists on the structure of the most common HDL protein, apolipoprotein (apo) A-I, in spheres vs. better studied discoidal forms. We produced spherical HDL by incubating reconstituted discoidal HDL with physiological plasma-remodeling enzymes and compared apoA-I structure in discs and spheres of comparable diameter (79–80 and 93–96 Å). Using cross-linking chemistry and mass spectrometry, we determined that the general structural organization of apoA-I was overall similar between discs and spheres, regardless of diameter. This was the case despite the fact that the 93 Å spheres contained three molecules of apoA-I per particle compared with only two in the discs. Thus, apoA-I adopts a consistent general structural framework in HDL particles—irrespective of shape, size and the number of apoA-Is present. Furthermore, a similar cross-linking pattern was demonstrated in HDL particles isolated from human serum. We propose the first experiment-based molecular model of apoA-I in spherical HDL particles. This model provides a new foundation for understanding how apoA-I structure modulates HDL function and metabolism.</p>
</abstract>
<kwd-group>
<kwd>sphere</kwd>
<kwd>disk</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>France</li>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Kansas</li>
<li>Nouvelle-Galles du Sud</li>
<li>Ohio</li>
<li>Tennessee</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Melbourne</li>
<li>Paris</li>
<li>Sydney</li>
</settlement>
<orgName>
<li>Université de Melbourne</li>
<li>Université de Sydney</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Ohio">
<name sortKey="Silva, R A Gangani D" sort="Silva, R A Gangani D" uniqKey="Silva R" first="R. A. Gangani D." last="Silva">R. A. Gangani D. Silva</name>
</region>
<name sortKey="Davidson, W Sean" sort="Davidson, W Sean" uniqKey="Davidson W" first="W. Sean" last="Davidson">W. Sean Davidson</name>
<name sortKey="Fang, Jianwen" sort="Fang, Jianwen" uniqKey="Fang J" first="Jianwen" last="Fang">Jianwen Fang</name>
<name sortKey="Gracheva, Elena O" sort="Gracheva, Elena O" uniqKey="Gracheva E" first="Elena O." last="Gracheva">Elena O. Gracheva</name>
<name sortKey="Huang, Rong" sort="Huang, Rong" uniqKey="Huang R" first="Rong" last="Huang">Rong Huang</name>
<name sortKey="Jerome, W Gray" sort="Jerome, W Gray" uniqKey="Jerome W" first="W. Gray" last="Jerome">W. Gray Jerome</name>
<name sortKey="Morris, Jamie" sort="Morris, Jamie" uniqKey="Morris J" first="Jamie" last="Morris">Jamie Morris</name>
<name sortKey="Ren, Gang" sort="Ren, Gang" uniqKey="Ren G" first="Gang" last="Ren">Gang Ren</name>
</country>
<country name="France">
<region name="Île-de-France">
<name sortKey="Kontush, Anatol" sort="Kontush, Anatol" uniqKey="Kontush A" first="Anatol" last="Kontush">Anatol Kontush</name>
</region>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Rye, Kerry Anne" sort="Rye, Kerry Anne" uniqKey="Rye K" first="Kerry-Anne" last="Rye">Kerry-Anne Rye</name>
</noRegion>
<name sortKey="Rye, Kerry Anne" sort="Rye, Kerry Anne" uniqKey="Rye K" first="Kerry-Anne" last="Rye">Kerry-Anne Rye</name>
<name sortKey="Rye, Kerry Anne" sort="Rye, Kerry Anne" uniqKey="Rye K" first="Kerry-Anne" last="Rye">Kerry-Anne Rye</name>
</country>
</tree>
</affiliations>
</record>

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