Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding
Identifieur interne : 007594 ( Main/Merge ); précédent : 007593; suivant : 007595Structural 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:
- https://api.istex.fr/document/AB5729DC76EAF891407A74B81AF7C8627DDA7FFB/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099469
DOI: 10.1038/sj.emboj.7601906
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<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>
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<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</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"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Desmarais, William" sort="Desmarais, William" uniqKey="Desmarais W" first="William" last="Desmarais">William Desmarais</name>
<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</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"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bagri, Anil" sort="Bagri, Anil" uniqKey="Bagri A" first="Anil" last="Bagri">Anil Bagri</name>
<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</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"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Research Drug Discovery, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</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"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name>
<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</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"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wiesmann, Christian" sort="Wiesmann, Christian" uniqKey="Wiesmann C" first="Christian" last="Wiesmann">Christian Wiesmann</name>
<affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., CA, South San Francisco</wicri:regionArea>
<wicri:noRegion>South San Francisco</wicri:noRegion>
</affiliation>
<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>
</ISTEX>
<PMC><TEI><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"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Ping" sort="Wu, Ping" uniqKey="Wu P" first="Ping" last="Wu">Ping Wu</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maloney, Janice" sort="Maloney, Janice" uniqKey="Maloney J" first="Janice" last="Maloney">Janice Maloney</name>
<affiliation wicri:level="1"><nlm:aff id="O2">Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yin, Jianping" sort="Yin, Jianping" uniqKey="Yin J" first="Jianping" last="Yin">Jianping Yin</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liang, Wei Ching" sort="Liang, Wei Ching" uniqKey="Liang W" first="Wei-Ching" last="Liang">Wei-Ching Liang</name>
<affiliation wicri:level="1"><nlm:aff id="O3">Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Stawicki, Scott" sort="Stawicki, Scott" uniqKey="Stawicki S" first="Scott" last="Stawicki">Scott Stawicki</name>
<affiliation wicri:level="1"><nlm:aff id="O3">Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mortara, Kyle" sort="Mortara, Kyle" uniqKey="Mortara K" first="Kyle" last="Mortara">Kyle Mortara</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O4">Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Desmarais, William" sort="Desmarais, William" uniqKey="Desmarais W" first="William" last="Desmarais">William Desmarais</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bagri, Anil" sort="Bagri, Anil" uniqKey="Bagri A" first="Anil" last="Bagri">Anil Bagri</name>
<affiliation wicri:level="1"><nlm:aff id="O2">Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tessier Lavigne, Marc" sort="Tessier Lavigne, Marc" uniqKey="Tessier Lavigne M" first="Marc" last="Tessier-Lavigne">Marc Tessier-Lavigne</name>
<affiliation wicri:level="1"><nlm:aff id="O5">Department of Research Drug Discovery, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Research Drug Discovery, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O4">Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name>
<affiliation wicri:level="1"><nlm:aff id="O3">Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O2">Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wiesmann, Christian" sort="Wiesmann, Christian" uniqKey="Wiesmann C" first="Christian" last="Wiesmann">Christian Wiesmann</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">17989695</idno>
<idno type="pmc">2099469</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099469</idno>
<idno type="RBID">PMC:2099469</idno>
<idno type="doi">10.1038/sj.emboj.7601906</idno>
<date when="2007">2007</date>
<idno type="wicri:Area/Pmc/Corpus">000042</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000042</idno>
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<idno type="wicri:Area/Pmc/Checkpoint">003A78</idno>
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<idno type="wicri:doubleKey">0261-4189:2007:Appleton B:structural:studies:of</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" 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"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Ping" sort="Wu, Ping" uniqKey="Wu P" first="Ping" last="Wu">Ping Wu</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maloney, Janice" sort="Maloney, Janice" uniqKey="Maloney J" first="Janice" last="Maloney">Janice Maloney</name>
<affiliation wicri:level="1"><nlm:aff id="O2">Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yin, Jianping" sort="Yin, Jianping" uniqKey="Yin J" first="Jianping" last="Yin">Jianping Yin</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liang, Wei Ching" sort="Liang, Wei Ching" uniqKey="Liang W" first="Wei-Ching" last="Liang">Wei-Ching Liang</name>
<affiliation wicri:level="1"><nlm:aff id="O3">Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Stawicki, Scott" sort="Stawicki, Scott" uniqKey="Stawicki S" first="Scott" last="Stawicki">Scott Stawicki</name>
<affiliation wicri:level="1"><nlm:aff id="O3">Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mortara, Kyle" sort="Mortara, Kyle" uniqKey="Mortara K" first="Kyle" last="Mortara">Kyle Mortara</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O4">Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Desmarais, William" sort="Desmarais, William" uniqKey="Desmarais W" first="William" last="Desmarais">William Desmarais</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bagri, Anil" sort="Bagri, Anil" uniqKey="Bagri A" first="Anil" last="Bagri">Anil Bagri</name>
<affiliation wicri:level="1"><nlm:aff id="O2">Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tessier Lavigne, Marc" sort="Tessier Lavigne, Marc" uniqKey="Tessier Lavigne M" first="Marc" last="Tessier-Lavigne">Marc Tessier-Lavigne</name>
<affiliation wicri:level="1"><nlm:aff id="O5">Department of Research Drug Discovery, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Research Drug Discovery, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O4">Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Yan" sort="Wu, Yan" uniqKey="Wu Y" first="Yan" last="Wu">Yan Wu</name>
<affiliation wicri:level="1"><nlm:aff id="O3">Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</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"><nlm:aff id="O2">Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Tumor Biology & Angiogenesis, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wiesmann, Christian" sort="Wiesmann, Christian" uniqKey="Wiesmann C" first="Christian" last="Wiesmann">Christian Wiesmann</name>
<affiliation wicri:level="1"><nlm:aff id="O1">Department of Protein Engineering, Genentech, Inc., South San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Protein Engineering, Genentech, Inc., South San Francisco, CA</wicri:regionArea>
<wicri:noRegion>CA</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">The EMBO Journal</title>
<idno type="ISSN">0261-4189</idno>
<idno type="eISSN">1460-2075</idno>
<imprint><date when="2007">2007</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>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 <italic>in vitro</italic>
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.</p>
</div>
</front>
</TEI>
</PMC>
</double>
</record>
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