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| | ==Neuropilin-1 b1 Domain in Complex with a VEGF-Blocking Fab== | | ==Neuropilin-1 b1 Domain in Complex with a VEGF-Blocking Fab== |
| - | <StructureSection load='2qqn' size='340' side='right' caption='[[2qqn]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='2qqn' size='340' side='right'caption='[[2qqn]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qqn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QQN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QQN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qqn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QQN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qqi|2qqi]], [[2qqj|2qqj]], [[2qqk|2qqk]], [[2qql|2qql]], [[2qqm|2qqm]], [[2qqo|2qqo]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NRP1, NRP, VEGF165R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qqn OCA], [https://pdbe.org/2qqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qqn RCSB], [https://www.ebi.ac.uk/pdbsum/2qqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qqn ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qqn OCA], [http://pdbe.org/2qqn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qqn RCSB], [http://www.ebi.ac.uk/pdbsum/2qqn PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NRP1_HUMAN NRP1_HUMAN]] The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis. The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity. | + | [https://www.uniprot.org/uniprot/NRP1_HUMAN NRP1_HUMAN] The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis. The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qq/2qqn_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qq/2qqn_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Antibody|Antibody]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | *[[Neuropilin|Neuropilin]] | | *[[Neuropilin|Neuropilin]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Appleton, B A]] | + | [[Category: Large Structures]] |
| - | [[Category: Wiesmann, C]] | + | [[Category: Appleton BA]] |
| - | [[Category: Angiogenesis]] | + | [[Category: Wiesmann C]] |
| - | [[Category: Developmental protein]]
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| - | [[Category: Differentiation]]
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| - | [[Category: Glycoprotein]]
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| - | [[Category: Heparan sulfate]]
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| - | [[Category: Hormone]]
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| - | [[Category: Membrane]]
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| - | [[Category: Neurogenesis]]
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| - | [[Category: Phage-derived antibody]]
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| - | [[Category: Proteoglycan]]
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| - | [[Category: Secreted]]
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| - | [[Category: Semaphorin receptor]]
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| - | [[Category: Signaling protein]]
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| - | [[Category: Transmembrane]]
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| - | [[Category: Vegf receptor]]
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| Structural highlights
Function
NRP1_HUMAN The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis. The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding.,Appleton BA, Wu P, Maloney J, Yin J, Liang WC, Stawicki S, Mortara K, Bowman KK, Elliott JM, Desmarais W, Bazan JF, Bagri A, Tessier-Lavigne M, Koch AW, Wu Y, Watts RJ, Wiesmann C EMBO J. 2007 Nov 28;26(23):4902-12. Epub 2007 Nov 8. PMID:17989695[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Appleton BA, Wu P, Maloney J, Yin J, Liang WC, Stawicki S, Mortara K, Bowman KK, Elliott JM, Desmarais W, Bazan JF, Bagri A, Tessier-Lavigne M, Koch AW, Wu Y, Watts RJ, Wiesmann C. Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding. EMBO J. 2007 Nov 28;26(23):4902-12. Epub 2007 Nov 8. PMID:17989695
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