View source for 4yn0


==Crystal structure of APP E2 domain in complex with DR6 CRD domain==
<StructureSection load='4yn0' size='340' side='right'caption='[[4yn0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yn0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YN0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YN0 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4yn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yn0 OCA], [https://pdbe.org/4yn0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yn0 RCSB], [https://www.ebi.ac.uk/pdbsum/4yn0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yn0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TNR21_MOUSE TNR21_MOUSE] Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B. Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm. Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). Negatively regulates oligodendrocyte survival, maturation and myelination. Plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation. Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells. Negatively regulates the production of IgG, IgM and IgM in response to antigens. May inhibit the activation of JNK in response to T-cell stimulation.<ref>PMID:11485735</ref> <ref>PMID:11714751</ref> <ref>PMID:12515813</ref> <ref>PMID:19225519</ref> <ref>PMID:21725297</ref> <ref>PMID:23559013</ref> 
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== Publication Abstract from PubMed ==
The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation.,Xu K, Olsen O, Tzvetkova-Robev D, Tessier-Lavigne M, Nikolov DB Genes Dev. 2015 Apr 2. PMID:25838500<ref>PMID:25838500</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 4yn0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Nikolov D]]
[[Category: Xu K]]