6xm2
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==The structure of the 4A11.v7 antibody in complex with human TGFb2== |
| - | <StructureSection load='6xm2' size='340' side='right'caption='[[6xm2]]' scene=''> | + | <StructureSection load='6xm2' size='340' side='right'caption='[[6xm2]], [[Resolution|resolution]] 1.91Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xm2]] 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=6XM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XM2 FirstGlance]. <br> |
| - | </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=6xm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xm2 OCA], [https://pdbe.org/6xm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xm2 RCSB], [https://www.ebi.ac.uk/pdbsum/6xm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xm2 ProSAT]</span></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]] 1.91Å</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=6xm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xm2 OCA], [https://pdbe.org/6xm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xm2 RCSB], [https://www.ebi.ac.uk/pdbsum/6xm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xm2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/TGFB2_HUMAN TGFB2_HUMAN] Note=A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9. Defects in TGFB2 are the cause of Loeys-Dietz syndrome 4 (LDS4) [MIM:[https://omim.org/entry/614816 614816]. An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.<ref>PMID:22772368</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TGFB2_HUMAN TGFB2_HUMAN] TGF-beta 2 has suppressive effects on interleukin-2 dependent T-cell growth. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Transforming growth factor-beta (TGFbeta) is a key driver of fibrogenesis. Three TGFbeta isoforms (TGFbeta1, TGFbeta2, and TGFbeta3) in mammals have distinct functions in embryonic development; however, the postnatal pathological roles and activation mechanisms of TGFbeta2 and TGFbeta3 have not been well characterized. Here, we show that the latent forms of TGFbeta2 and TGFbeta3 can be activated by integrin-independent mechanisms and have lower activation thresholds compared to TGFbeta1. Unlike TGFB1, TGFB2 and TGFB3 expression is increased in human lung and liver fibrotic tissues compared to healthy control tissues. Thus, TGFbeta2 and TGFbeta3 may play a pathological role in fibrosis. Inducible conditional knockout mice and anti-TGFbeta isoform-selective antibodies demonstrated that TGFbeta2 and TGFbeta3 are independently involved in mouse fibrosis models in vivo, and selective TGFbeta2 and TGFbeta3 inhibition does not lead to the increased inflammation observed with pan-TGFbeta isoform inhibition. A cocrystal structure of a TGFbeta2-anti-TGFbeta2/3 antibody complex reveals an allosteric isoform-selective inhibitory mechanism. Therefore, inhibiting TGFbeta2 and/or TGFbeta3 while sparing TGFbeta1 may alleviate fibrosis without toxicity concerns associated with pan-TGFbeta blockade. | ||
| + | |||
| + | TGFbeta2 and TGFbeta3 isoforms drive fibrotic disease pathogenesis.,Sun T, Huang Z, Liang WC, Yin J, Lin WY, Wu J, Vernes JM, Lutman J, Caplazi P, Jeet S, Wong T, Wong M, DePianto DJ, Morshead KB, Sun KH, Modrusan Z, Vander Heiden JA, Abbas AR, Zhang H, Xu M, N'Diaye EN, Roose-Girma M, Wolters PJ, Yadav R, Sukumaran S, Ghilardi N, Corpuz R, Emson C, Meng YG, Ramalingam TR, Lupardus P, Brightbill HD, Seshasayee D, Wu Y, Arron JR Sci Transl Med. 2021 Aug 4;13(605):eabe0407. doi: 10.1126/scitranslmed.abe0407. PMID:34349032<ref>PMID:34349032</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6xm2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Lupardus PJ]] |
| + | [[Category: Yin JP]] | ||
Current revision
The structure of the 4A11.v7 antibody in complex with human TGFb2
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