View source for 4kv5


==scFv GC1009 in complex with TGF-beta1.==
<StructureSection load='4kv5' size='340' side='right'caption='[[4kv5]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kv5]] is a 8 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=4KV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KV5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</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=4kv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kv5 OCA], [https://pdbe.org/4kv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kv5 RCSB], [https://www.ebi.ac.uk/pdbsum/4kv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kv5 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN] Defects in TGFB1 are the cause of Camurati-Engelmann disease (CE) [MIM:[https://omim.org/entry/131300 131300]; also known as progressive diaphyseal dysplasia 1 (DPD1). CE is an autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision.<ref>PMID:10973241</ref> <ref>PMID:11062463</ref> <ref>PMID:12493741</ref> <ref>PMID:12843182</ref> <ref>PMID:15103729</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TGFB1_HUMAN TGFB1_HUMAN] Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts.
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== Publication Abstract from PubMed ==
Various important biological pathways are modulated by TGFbeta isoforms; as such they are potential targets for therapeutic intervention. Fresolimumab, also known as GC1008, is a pan-TGFbeta neutralizing antibody that has been tested clinically for several indications including an ongoing trial for focal segmental glomerulosclerosis. The structure of the antigen-binding fragment of fresolimumab (GC1008 Fab) in complex with TGFbeta3 has been reported previously, but the structural capacity of fresolimumab to accommodate tight interactions with TGFbeta1 and TGFbeta2 was insufficiently understood. We report the crystal structure of the single-chain variable fragment of fresolimumab (GC1008 scFv) in complex with target TGFbeta1 to a resolution of 3.00 A and the crystal structure of GC1008 Fab in complex with TGFbeta2 to 2.83 A. The structures provide further insight into the details of TGFbeta recognition by fresolimumab, give a clear indication of the determinants of fresolimumab pan-specificity and provide potential starting points for the development of isoform-specific antibodies using a fresolimumab scaffold.

Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFbeta reveal structural plasticity of antibody-antigen interactions.,Moulin A, Mathieu M, Lawrence C, Bigelow R, Levine M, Hamel C, Marquette JP, Le Parc J, Loux C, Ferrari P, Capdevila C, Dumas J, Dumas B, Rak A, Bird J, Qiu H, Pan CQ, Edmunds T, Wei RR Protein Sci. 2014 Sep 10. doi: 10.1002/pro.2548. PMID:25209176<ref>PMID:25209176</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4kv5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[3D structures of human antibody|3D structures of human antibody]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mathieu M]]
[[Category: Moulin AG]]
[[Category: Wei R]]