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| | <StructureSection load='6i9j' size='340' side='right'caption='[[6i9j]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6i9j' size='340' side='right'caption='[[6i9j]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i9j]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I9J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i9j]] is a 1 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=6I9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9J 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=6i9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9j OCA], [http://pdbe.org/6i9j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i9j RCSB], [http://www.ebi.ac.uk/pdbsum/6i9j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9j 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]] 2Å</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=6i9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9j OCA], [https://pdbe.org/6i9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9j RCSB], [https://www.ebi.ac.uk/pdbsum/6i9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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:[http://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> | + | [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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TGFB2_HUMAN TGFB2_HUMAN]] TGF-beta 2 has suppressive effects on interleukin-2 dependent T-cell growth. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Amo-Maestro, L del]]
| + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Goulas T]] |
| - | [[Category: Goulas, T]] | + | [[Category: Marino-Puertas L]] |
| - | [[Category: Marino-Puertas, L]] | + | [[Category: Del Amo-Maestro L]] |
| - | [[Category: Cell growth]] | + | |
| - | [[Category: Cysteine-knot cytokine]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Growth factor]]
| + | |
| - | [[Category: Small protein]]
| + | |
| - | [[Category: Tgf-beta2]]
| + | |
| Structural highlights
Disease
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: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.[1]
Function
TGFB2_HUMAN TGF-beta 2 has suppressive effects on interleukin-2 dependent T-cell growth.
Publication Abstract from PubMed
Transforming growth factor beta is a disulfide-linked dimeric cytokine that occurs in three highly related isoforms (TGFbeta1-TGFbeta3) engaged in signaling functions through binding of cognate TGFbeta receptors. To regulate this pathway, the cytokines are biosynthesized as inactive pro-TGFbetas with an N-terminal latency-associated protein preceding the mature moieties. Due to their pleiotropic implications in physiology and pathology, TGFbetas are privileged objects of in vitro studies. However, such studies have long been limited by the lack of efficient human recombinant expression systems of native, glycosylated, and homogenous proteins. Here, we developed pro-TGFbeta2 production systems based on human Expi293F cells, which yielded >2 mg of pure histidine- or Strep-tagged protein per liter of cell culture. We assayed this material biophysically and in crystallization assays and obtained a different crystal form of mature TGFbeta2, which adopted a conformation deviating from previous structures, with a distinct dimeric conformation that would require significant rearrangement for binding of TGFbeta receptors. This new conformation may be reversibly adopted by a certain fraction of the mature TGbeta2 population and represent a hitherto undescribed additional level of activity regulation of the mature growth factor once the latency-associated protein has been separated.
Recombinant production, purification, crystallization, and structure analysis of human transforming growth factor beta2 in a new conformation.,Del Amo-Maestro L, Marino-Puertas L, Goulas T, Gomis-Ruth FX Sci Rep. 2019 Jun 17;9(1):8660. doi: 10.1038/s41598-019-44943-4. PMID:31209258[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, Kempers MJ, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL. Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet. 2012 Jul 8;44(8):922-7. doi: 10.1038/ng.2349. PMID:22772368 doi:10.1038/ng.2349
- ↑ Del Amo-Maestro L, Marino-Puertas L, Goulas T, Gomis-Ruth FX. Recombinant production, purification, crystallization, and structure analysis of human transforming growth factor beta2 in a new conformation. Sci Rep. 2019 Jun 17;9(1):8660. doi: 10.1038/s41598-019-44943-4. PMID:31209258 doi:http://dx.doi.org/10.1038/s41598-019-44943-4
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