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| | ==PDGF-B blocking antibody bound to PDGF-BB== | | ==PDGF-B blocking antibody bound to PDGF-BB== |
| - | <StructureSection load='4qci' size='340' side='right' caption='[[4qci]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4qci' size='340' side='right'caption='[[4qci]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qci]] is a 6 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=4QCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QCI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qci]] is a 6 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=4QCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QCI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDGFB, PDGF2, SIS ([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]] 2.3Å</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=4qci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qci OCA], [http://pdbe.org/4qci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qci RCSB], [http://www.ebi.ac.uk/pdbsum/4qci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qci 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=4qci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qci OCA], [https://pdbe.org/4qci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qci RCSB], [https://www.ebi.ac.uk/pdbsum/4qci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qci ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PDGFB_HUMAN PDGFB_HUMAN]] Note=A chromosomal aberration involving PDGFB is found in dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with PDGFB.<ref>PMID:12660034</ref> | + | [https://www.uniprot.org/uniprot/PDGFB_HUMAN PDGFB_HUMAN] Note=A chromosomal aberration involving PDGFB is found in dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with PDGFB.<ref>PMID:12660034</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDGFB_HUMAN PDGFB_HUMAN]] Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA (By similarity). | + | [https://www.uniprot.org/uniprot/PDGFB_HUMAN PDGFB_HUMAN] Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA (By similarity). |
| | <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 4qci" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4qci" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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: Carven, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Kuai, J]] | + | [[Category: Carven G]] |
| - | [[Category: LaVallie, E]] | + | [[Category: Kuai J]] |
| - | [[Category: Mosyak, L]] | + | [[Category: LaVallie E]] |
| - | [[Category: Pullen, N]] | + | [[Category: Mosyak L]] |
| - | [[Category: Tam, M]] | + | [[Category: Pullen N]] |
| - | [[Category: Cytokine-cytokine receptor complex]]
| + | [[Category: Tam M]] |
| - | [[Category: Extracellular]]
| + | |
| - | [[Category: Growth factor cytokine fold]]
| + | |
| - | [[Category: Growth factor hormone]]
| + | |
| - | [[Category: Pdgfr-beta receptor]]
| + | |
| Structural highlights
Disease
PDGFB_HUMAN Note=A chromosomal aberration involving PDGFB is found in dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with PDGFB.[1]
Function
PDGFB_HUMAN Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA (By similarity).
Publication Abstract from PubMed
Platelet derived growth factor-BB (PDGF-BB) is an important mitogen and cell survival factor during development. PDGF-BB binds PDGF receptor-beta (PDGFRbeta) to trigger receptor dimerization and tyrosine kinase activation. We present the pharmacological and biophysical characterization of a blocking PDGF-BB monoclonal antibody, MOR8457, and contrast this to PDGFRbeta. MOR8457 binds to PDGF-BB with high affinity and selectivity, and prevents PDGF-BB induced cell proliferation competitively and with high potency. The structural characterization of the MOR8457-PDGF-BB complex indicates that MOR8457 binds with a 2:1 stoichiometry, but that binding of a single MOR8457 moiety is sufficient to prevent binding to PDGFRbeta. Comparison of the MOR8457-PDGF-BB structure with that of the PDGFRbeta-PDGF-BB complex suggested the potential reason for this was a substantial bending and twisting of PDGF-BB in the MOR8457 structure, relative to the structures of PDGF-BB alone, bound to a PDGF-BB aptamer or PDGFRbeta, which makes it nonpermissive for PDGFRbeta binding. These biochemical and structural data offer insights into the permissive structure of PDGF-BB needed for agonism as well as strategies for developing specific PDGF ligand antagonists.
Characterization of Binding Mode of Action of a Blocking Anti-Platelet-Derived Growth Factor (PDGF)-B Monoclonal Antibody, MOR8457, Reveals Conformational Flexibility and Avidity Needed for PDGF-BB To Bind PDGF Receptor-beta,Kuai J, Mosyak L, Brooks J, Cain M, Carven GJ, Ogawa S, Ishino T, Tam M, Lavallie ER, Yang Z, Ponsel D, Rauchenberger R, Arch R, Pullen N Biochemistry. 2015 Mar 6. PMID:25707433[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sandberg AA, Anderson WD, Fredenberg C, Hashimoto H. Dermatofibrosarcoma protuberans of breast. Cancer Genet Cytogenet. 2003 Apr 1;142(1):56-9. PMID:12660034
- ↑ Kuai J, Mosyak L, Brooks J, Cain M, Carven GJ, Ogawa S, Ishino T, Tam M, Lavallie ER, Yang Z, Ponsel D, Rauchenberger R, Arch R, Pullen N. Characterization of Binding Mode of Action of a Blocking Anti-Platelet-Derived Growth Factor (PDGF)-B Monoclonal Antibody, MOR8457, Reveals Conformational Flexibility and Avidity Needed for PDGF-BB To Bind PDGF Receptor-beta Biochemistry. 2015 Mar 6. PMID:25707433 doi:http://dx.doi.org/10.1021/bi5015425
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