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| | <StructureSection load='6osh' size='340' side='right'caption='[[6osh]], [[Resolution|resolution]] 1.12Å' scene=''> | | <StructureSection load='6osh' size='340' side='right'caption='[[6osh]], [[Resolution|resolution]] 1.12Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6osh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OSH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OSH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6osh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OSH FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ROR2, NTRKR2 ([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]] 1.117Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=6osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6osh OCA], [https://pdbe.org/6osh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6osh RCSB], [https://www.ebi.ac.uk/pdbsum/6osh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6osh ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6osh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6osh OCA], [http://pdbe.org/6osh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6osh RCSB], [http://www.ebi.ac.uk/pdbsum/6osh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6osh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ROR2_HUMAN ROR2_HUMAN]] Autosomal recessive Robinow syndrome;Brachydactyly type B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/ROR2_HUMAN ROR2_HUMAN] Autosomal recessive Robinow syndrome;Brachydactyly type B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ROR2_HUMAN ROR2_HUMAN]] Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development. Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation.<ref>PMID:17717073</ref> | + | [https://www.uniprot.org/uniprot/ROR2_HUMAN ROR2_HUMAN] Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development. Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation.<ref>PMID:17717073</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6osh" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6osh" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: European rabbit]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Receptor protein-tyrosine kinase]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Park, H]] | + | [[Category: Park H]] |
| - | [[Category: Rader, C]] | + | [[Category: Rader C]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Kringle domain]]
| + | |
| - | [[Category: Phage display]]
| + | |
| - | [[Category: Receptor tyrosine kinase-like orphan receptor]]
| + | |
| - | [[Category: Ror2]]
| + | |
| - | [[Category: Scfv]]
| + | |
| - | [[Category: Single chain fv]]
| + | |
| Structural highlights
Disease
ROR2_HUMAN Autosomal recessive Robinow syndrome;Brachydactyly type B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
ROR2_HUMAN Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development. Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation.[1]
Publication Abstract from PubMed
Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues, but is up-regulated in a diverse set of hematologic and solid malignancies. Thus, ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning, and again co-crystallized with hROR2-Kr. We show that the affinity matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T-cell engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.
Affinity maturation, humanization, and co-crystallization of a rabbit anti-human ROR2 monoclonal antibody for therapeutic applications.,Goydel RS, Weber J, Peng H, Qi J, Soden J, Freeth J, Park H, Rader C J Biol Chem. 2020 Mar 19. pii: RA120.012791. doi: 10.1074/jbc.RA120.012791. PMID:32193207[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu Y, Ross JF, Bodine PV, Billiard J. Homodimerization of Ror2 tyrosine kinase receptor induces 14-3-3(beta) phosphorylation and promotes osteoblast differentiation and bone formation. Mol Endocrinol. 2007 Dec;21(12):3050-61. Epub 2007 Aug 23. PMID:17717073 doi:http://dx.doi.org/10.1210/me.2007-0323
- ↑ Goydel RS, Weber J, Peng H, Qi J, Soden J, Freeth J, Park H, Rader C. Affinity maturation, humanization, and co-crystallization of a rabbit anti-human ROR2 monoclonal antibody for therapeutic applications. J Biol Chem. 2020 Mar 19. pii: RA120.012791. doi: 10.1074/jbc.RA120.012791. PMID:32193207 doi:http://dx.doi.org/10.1074/jbc.RA120.012791
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