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4qci

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Revision as of 17:02, 4 January 2017

PDGF-B blocking antibody bound to PDGF-BB

Structural highlights

4qci is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qci"

@@ Line 1: / Line 1: @@
 ==PDGF-B blocking antibody bound to PDGF-BB==
 <StructureSection load='4qci' size='340' side='right' caption='[[4qci]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4qci]] is a 6 chain structure. 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>
-</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://www.rcsb.org/pdb/explore.do?structureId=4qci RCSB], [http://www.ebi.ac.uk/pdbsum/4qci PDBsum]</span></td></tr>
+</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>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4qci" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4qci

From Proteopedia

Revision as of 17:02, 4 January 2017

PDGF-B blocking antibody bound to PDGF-BB

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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