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| | ==Solution structure of C-terminal domain of TRADD== | | ==Solution structure of C-terminal domain of TRADD== |
| - | <StructureSection load='5xme' size='340' side='right'caption='[[5xme]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='5xme' size='340' side='right'caption='[[5xme]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xme]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XME OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XME FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xme]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XME OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XME FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xme OCA], [http://pdbe.org/5xme PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xme RCSB], [http://www.ebi.ac.uk/pdbsum/5xme PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xme ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=5xme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xme OCA], [https://pdbe.org/5xme PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xme RCSB], [https://www.ebi.ac.uk/pdbsum/5xme PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xme ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRADD_HUMAN TRADD_HUMAN]] The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A (By similarity). Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B. | + | [https://www.uniprot.org/uniprot/TRADD_HUMAN TRADD_HUMAN] The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A (By similarity). Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | The TNFR1-associated death domain protein (TRADD) is an intracellular adaptor protein involved in various signaling pathways, such as antiapoptosis. Its C-terminal death domain (DD) is responsible for binding other DD-containing proteins including the p75 neurotrophin receptor (p75NTR). Here we present a solution structure of TRADD DD derived from high-resolution NMR spectroscopy. The TRADD DD comprises two super-secondary structures, an all-helix Greek key motif and a beta-hairpin motif flanked by two alpha helices, which make it unique among all known DD structures. The beta-hairpin motif is essential for TRADD DD to fold into a functional globular domain. The highly-charged surface suggests a critical role of electrostatic interactions in TRADD DD-mediated signaling. This novel structure represents a new class within the DD superfamily and provides a structural basis for studying homotypic DD interactions. NMR titration revealed a direct weak interaction between TRADD DD and p75NTR DD monomers. A binding site next to the p75NTR DD homodimerization interface indicates that TRADD DD recruitment to p75NTR requires separation of the p75NTR DD homodimer, explaining the mechanism of NGF-dependent activation of p75NTR-TRADD-mediated antiapoptotic pathway in breast cancer cell.
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| - | Structure of the C-terminal domain of TRADD reveals a novel fold in the death domain superfamily.,Zhang N, Yuan W, Fan JS, Lin Z Sci Rep. 2017 Aug 1;7(1):7073. doi: 10.1038/s41598-017-07348-9. PMID:28765645<ref>PMID:28765645</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5xme" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lin, Z]] | + | [[Category: Lin Z]] |
| - | [[Category: Zhang, N]] | + | [[Category: Zhang N]] |
| - | [[Category: Apoptosis]]
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| - | [[Category: Death domain]]
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| - | [[Category: Tradd]]
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