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| <StructureSection load='6ba5' size='340' side='right'caption='[[6ba5]], [[Resolution|resolution]] 1.62Å' scene=''> | | <StructureSection load='6ba5' size='340' side='right'caption='[[6ba5]], [[Resolution|resolution]] 1.62Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6ba5]] is a 12 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=6BA5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BA5 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6ba5]] is a 12 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=6BA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BA5 FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ROR1, NTRKR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.62Å</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=6ba5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ba5 OCA], [http://pdbe.org/6ba5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ba5 RCSB], [http://www.ebi.ac.uk/pdbsum/6ba5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ba5 ProSAT]</span></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=6ba5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ba5 OCA], [https://pdbe.org/6ba5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ba5 RCSB], [https://www.ebi.ac.uk/pdbsum/6ba5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ba5 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/ROR1_HUMAN ROR1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | | [https://www.uniprot.org/uniprot/ROR1_HUMAN ROR1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/ROR1_HUMAN ROR1_HUMAN]] Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350).<ref>PMID:25029443</ref> <ref>PMID:27162350</ref> | | [https://www.uniprot.org/uniprot/ROR1_HUMAN ROR1_HUMAN] Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350).<ref>PMID:25029443</ref> <ref>PMID:27162350</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
| |
| T cell-engaging bispecific antibodies (biAbs) present a promising strategy for cancer immunotherapy, and numerous bispecific formats have been developed for retargeting cytolytic T cells toward tumor cells. To explore the therapeutic utility of T cell-engaging biAbs targeting the receptor tyrosine kinase ROR1, which is expressed by tumor cells of various hematologic and solid malignancies, we used a bispecific ROR1 x CD3 scFv-Fc format based on a heterodimeric and aglycosylated Fc domain designed for extended circulatory t1/2 and diminished systemic T cell activation. A diverse panel of ROR1-targeting scFv derived from immune and naive rabbit antibody repertoires was compared in this bispecific format for target-dependent T cell recruitment and activation. An ROR1-targeting scFv with a membrane-proximal epitope, R11, revealed potent and selective antitumor activity in vitro, in vivo, and ex vivo and emerged as a prime candidate for further preclinical and clinical studies. To elucidate the precise location and engagement of this membrane-proximal epitope, which is conserved between human and mouse ROR1, the 3D structure of scFv R11 in complex with the kringle domain of ROR1 was determined by X-ray crystallography at 1.6-A resolution.
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| Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1.,Qi J, Li X, Peng H, Cook EM, Dadashian EL, Wiestner A, Park H, Rader C Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5467-E5476. doi:, 10.1073/pnas.1719905115. Epub 2018 May 29. PMID:29844189<ref>PMID:29844189</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6ba5" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | *[[3D structures of human antibody|3D structures of human antibody]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Park, H]] | | [[Category: Park H]] |
| [[Category: Rader, C]] | | [[Category: Rader C]] |
| [[Category: Antibody]]
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| [[Category: Immune system]]
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| [[Category: Kringle domain]]
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| [[Category: Phage display]]
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| [[Category: Receptor tyrosine kinase-like orphan receptor]]
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| [[Category: Ror1]]
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| [[Category: Scfv]]
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| [[Category: Single chain fv]]
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