Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding
Identifieur interne : 005059 ( Istex/Curation ); précédent : 005058; suivant : 005060Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding
Auteurs : Brent A. Appleton [États-Unis] ; Ping Wu [États-Unis] ; Janice Maloney [États-Unis] ; Jianping Yin [États-Unis] ; Wei-Ching Liang [États-Unis] ; Scott Stawicki [États-Unis] ; Kyle Mortara [États-Unis] ; Krista K. Bowman [États-Unis] ; J Michael Elliott [États-Unis] ; William Desmarais [États-Unis] ; J Fernando Bazan [États-Unis] ; Anil Bagri [États-Unis] ; Marc Tessier-Lavigne [États-Unis] ; Alexander W. Koch [États-Unis] ; Yan Wu [États-Unis] ; Ryan J. Watts [États-Unis] ; Christian Wiesmann [États-Unis]Source :
- The EMBO Journal [ 0261-4189 ] ; 2007-11-28.
Abstract
Neuropilins (Nrps) are co‐receptors for class 3 semaphorins and vascular endothelial growth factors and important for the development of the nervous system and the vasculature. The extracellular portion of Nrp is composed of two domains that are essential for semaphorin binding (a1a2), two domains necessary for VEGF binding (b1b2), and one domain critical for receptor dimerization (c). We report several crystal structures of Nrp1 and Nrp2 fragments alone and in complex with antibodies that selectively block either semaphorin or vascular endothelial growth factor (VEGF) binding. In these structures, Nrps adopt an unexpected domain arrangement in which the a2, b1, and b2 domains form a tightly packed core that is only loosely connected to the a1 domain. The locations of the antibody epitopes together with in vitro experiments indicate that VEGF and semaphorin do not directly compete for Nrp binding. Based upon our structural and functional data, we propose possible models for ligand binding to neuropilins.
Url:
DOI: 10.1038/sj.emboj.7601906
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :005059
Links to Exploration step
ISTEX:AB5729DC76EAF891407A74B81AF7C8627DDA7FFBLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding</title>
<author><name sortKey="Appleton, Brent A" sort="Appleton, Brent A" uniqKey="Appleton B" first="Brent A" last="Appleton">Brent A. Appleton</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Ping" sort="Wu, Ping" uniqKey="Wu P" first="Ping" last="Wu">Ping Wu</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Janice" sort="Maloney, Janice" uniqKey="Maloney J" first="Janice" last="Maloney">Janice Maloney</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yin, Jianping" sort="Yin, Jianping" uniqKey="Yin J" first="Jianping" last="Yin">Jianping Yin</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Liang, Wei Hing" sort="Liang, Wei Hing" uniqKey="Liang W" first="Wei-Ching" last="Liang">Wei-Ching Liang</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stawicki, Scott" sort="Stawicki, Scott" uniqKey="Stawicki S" first="Scott" last="Stawicki">Scott Stawicki</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mortara, Kyle" sort="Mortara, Kyle" uniqKey="Mortara K" first="Kyle" last="Mortara">Kyle Mortara</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bowman, Krista K" sort="Bowman, Krista K" uniqKey="Bowman K" first="Krista K" last="Bowman">Krista K. Bowman</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Elliott, J Michael" sort="Elliott, J Michael" uniqKey="Elliott J" first="J Michael" last="Elliott">J Michael Elliott</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Desmarais, William" sort="Desmarais, William" uniqKey="Desmarais W" first="William" last="Desmarais">William Desmarais</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bazan, J Fernando" sort="Bazan, J Fernando" uniqKey="Bazan J" first="J Fernando" last="Bazan">J Fernando Bazan</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bagri, Anil" sort="Bagri, Anil" uniqKey="Bagri A" first="Anil" last="Bagri">Anil Bagri</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tessier Avigne, Marc" sort="Tessier Avigne, Marc" uniqKey="Tessier Avigne M" first="Marc" last="Tessier-Lavigne">Marc Tessier-Lavigne</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Research Drug Discovery, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Research Drug Discovery, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Koch, Alexander W" sort="Koch, Alexander W" uniqKey="Koch A" first="Alexander W" last="Koch">Alexander W. Koch</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Watts, Ryan J" sort="Watts, Ryan J" uniqKey="Watts R" first="Ryan J" last="Watts">Ryan J. Watts</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wiesmann, Christian" sort="Wiesmann, Christian" uniqKey="Wiesmann C" first="Christian" last="Wiesmann">Christian Wiesmann</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
<affiliation><mods:affiliation>E-mail: chw@gene.com</mods:affiliation>
<wicri:noCountry code="no comma">E-mail: chw@gene.com</wicri:noCountry>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:AB5729DC76EAF891407A74B81AF7C8627DDA7FFB</idno>
<date when="2007" year="2007">2007</date>
<idno type="doi">10.1038/sj.emboj.7601906</idno>
<idno type="url">https://api.istex.fr/document/AB5729DC76EAF891407A74B81AF7C8627DDA7FFB/fulltext/pdf</idno>
<idno type="wicri:Area/Istex/Corpus">005059</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">005059</idno>
<idno type="wicri:Area/Istex/Curation">005059</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main">Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding</title>
<author><name sortKey="Appleton, Brent A" sort="Appleton, Brent A" uniqKey="Appleton B" first="Brent A" last="Appleton">Brent A. Appleton</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Ping" sort="Wu, Ping" uniqKey="Wu P" first="Ping" last="Wu">Ping Wu</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Maloney, Janice" sort="Maloney, Janice" uniqKey="Maloney J" first="Janice" last="Maloney">Janice Maloney</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yin, Jianping" sort="Yin, Jianping" uniqKey="Yin J" first="Jianping" last="Yin">Jianping Yin</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Liang, Wei Hing" sort="Liang, Wei Hing" uniqKey="Liang W" first="Wei-Ching" last="Liang">Wei-Ching Liang</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stawicki, Scott" sort="Stawicki, Scott" uniqKey="Stawicki S" first="Scott" last="Stawicki">Scott Stawicki</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mortara, Kyle" sort="Mortara, Kyle" uniqKey="Mortara K" first="Kyle" last="Mortara">Kyle Mortara</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bowman, Krista K" sort="Bowman, Krista K" uniqKey="Bowman K" first="Krista K" last="Bowman">Krista K. Bowman</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Elliott, J Michael" sort="Elliott, J Michael" uniqKey="Elliott J" first="J Michael" last="Elliott">J Michael Elliott</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Desmarais, William" sort="Desmarais, William" uniqKey="Desmarais W" first="William" last="Desmarais">William Desmarais</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bazan, J Fernando" sort="Bazan, J Fernando" uniqKey="Bazan J" first="J Fernando" last="Bazan">J Fernando Bazan</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bagri, Anil" sort="Bagri, Anil" uniqKey="Bagri A" first="Anil" last="Bagri">Anil Bagri</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tessier Avigne, Marc" sort="Tessier Avigne, Marc" uniqKey="Tessier Avigne M" first="Marc" last="Tessier-Lavigne">Marc Tessier-Lavigne</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Research Drug Discovery, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Research Drug Discovery, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Koch, Alexander W" sort="Koch, Alexander W" uniqKey="Koch A" first="Alexander W" last="Koch">Alexander W. Koch</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Watts, Ryan J" sort="Watts, Ryan J" uniqKey="Watts R" first="Ryan J" last="Watts">Ryan J. Watts</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wiesmann, Christian" sort="Wiesmann, Christian" uniqKey="Wiesmann C" first="Christian" last="Wiesmann">Christian Wiesmann</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco, USA</mods:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
</affiliation>
<affiliation><mods:affiliation>E-mail: chw@gene.com</mods:affiliation>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j" type="main">The EMBO Journal</title>
<title level="j" type="alt">THE EMBO JOURNAL</title>
<idno type="ISSN">0261-4189</idno>
<idno type="eISSN">1460-2075</idno>
<imprint><biblScope unit="vol">26</biblScope>
<biblScope unit="issue">23</biblScope>
<biblScope unit="page" from="4902">4902</biblScope>
<biblScope unit="page" to="4912">4912</biblScope>
<biblScope unit="page-count">11</biblScope>
<publisher>John Wiley & Sons, Ltd</publisher>
<pubPlace>Chichester, UK</pubPlace>
<date type="published" when="2007-11-28">2007-11-28</date>
</imprint>
<idno type="ISSN">0261-4189</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0261-4189</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract">Neuropilins (Nrps) are co‐receptors for class 3 semaphorins and vascular endothelial growth factors and important for the development of the nervous system and the vasculature. The extracellular portion of Nrp is composed of two domains that are essential for semaphorin binding (a1a2), two domains necessary for VEGF binding (b1b2), and one domain critical for receptor dimerization (c). We report several crystal structures of Nrp1 and Nrp2 fragments alone and in complex with antibodies that selectively block either semaphorin or vascular endothelial growth factor (VEGF) binding. In these structures, Nrps adopt an unexpected domain arrangement in which the a2, b1, and b2 domains form a tightly packed core that is only loosely connected to the a1 domain. The locations of the antibody epitopes together with in vitro experiments indicate that VEGF and semaphorin do not directly compete for Nrp binding. Based upon our structural and functional data, we propose possible models for ligand binding to neuropilins.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 005059 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 005059 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Istex |étape= Curation |type= RBID |clé= ISTEX:AB5729DC76EAF891407A74B81AF7C8627DDA7FFB |texte= Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding }}
![]() | This area was generated with Dilib version V0.6.31. | ![]() |