View source for 5nqh


==Structure of the human Fe65-PTB2 homodimer==
<StructureSection load='5nqh' size='340' side='right'caption='[[5nqh]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nqh]] is a 4 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=5NQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NQH 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5nqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nqh OCA], [https://pdbe.org/5nqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nqh RCSB], [https://www.ebi.ac.uk/pdbsum/5nqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nqh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/APBB1_HUMAN APBB1_HUMAN] Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. Function in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s).<ref>PMID:15031292</ref> <ref>PMID:18468999</ref> <ref>PMID:18922798</ref> <ref>PMID:19234442</ref> <ref>PMID:19343227</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 A resolution. Dimerization involves the unwinding of a C-terminal alpha-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.,Feilen LP, Haubrich K, Strecker P, Probst S, Eggert S, Stier G, Sinning I, Konietzko U, Kins S, Simon B, Wild K Front Mol Neurosci. 2017 May 11;10:140. doi: 10.3389/fnmol.2017.00140., eCollection 2017. PMID:28553201<ref>PMID:28553201</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nqh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Feilen LP]]
[[Category: Haubrich K]]
[[Category: Kins S]]
[[Category: Konietzko U]]
[[Category: Simon B]]
[[Category: Sinning I]]
[[Category: Wild K]]