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[[Image:2idh.jpg|left|200px]]


{{Structure
==Crystal Structure of human FE65 WW domain==
|PDB= 2idh |SIZE=350|CAPTION= <scene name='initialview01'>2idh</scene>, resolution 2.28&Aring;
<StructureSection load='2idh' size='340' side='right'caption='[[2idh]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=PG4:TETRAETHYLENE GLYCOL'>PG4</scene>
<table><tr><td colspan='2'>[[2idh]] is a 8 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=2IDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IDH FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.28&#8491;</td></tr>
|GENE= APBB1, FE65 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=2idh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2idh OCA], [https://pdbe.org/2idh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2idh RCSB], [https://www.ebi.ac.uk/pdbsum/2idh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2idh ProSAT]</span></td></tr>
 
</table>
'''Crystal Structure of human FE65 WW domain'''
== 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>
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
The neuronal protein FE65 functions in brain development and amyloid precursor protein (APP) signaling through its interaction with the mammalian enabled (Mena) protein and APP, respectively. The recognition of short polyproline sequences in Mena by the FE65 WW domain has a central role in axon guidance and neuronal positioning in the developing brain. We have determined the crystal structures of the human FE65 WW domain (residues 253-289) in the apo form and bound to the peptides PPPPPPLPP and PPPPPPPPPL, which correspond to human Mena residues 313-321 and 347-356, respectively. The FE65 WW domain contains two parallel ligand-binding grooves, XP (formed by residues Y269 and W280) and XP2 (formed by Y269 and W271). Both Mena peptides adopt a polyproline helical II conformation and bind to the WW domain in a forward (N-C) orientation through selection of the PPPPP motif by the XP and XP2 grooves. This mode of ligand recognition is strikingly similar to polyproline interaction with SH3 domains. Importantly, comparison of the FE65 WW structures in the apo and liganded forms shows that the XP2 groove is formed by an induced-fit mechanism that involves movements of the W271 and Y269 side-chains upon ligand binding. These structures elucidate the molecular determinants underlying polyproline ligand selection by the FE65 WW domain and provide a framework for the design of small molecules that would interfere with FE65 WW-ligand interaction and modulate neuronal development and APP signaling.
Check<jmol>
 
  <jmolCheckbox>
==Disease==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/id/2idh_consurf.spt"</scriptWhenChecked>
Known disease associated with this structure: Alzheimer disease, late-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602710 602710]]
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==About this Structure==
  </jmolCheckbox>
2IDH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IDH OCA].  
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2idh ConSurf].
 
<div style="clear:both"></div>
==Reference==
== References ==
Structural basis for polyproline recognition by the FE65 WW domain., Meiyappan M, Birrane G, Ladias JA, J Mol Biol. 2007 Sep 28;372(4):970-80. Epub 2007 Jun 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17686488 17686488]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Birrane, G.]]
[[Category: Birrane G]]
[[Category: Ladias, J A.A.]]
[[Category: Ladias JAA]]
[[Category: Meiyappan, M.]]
[[Category: Meiyappan M]]
[[Category: PG4]]
[[Category: SO4]]
[[Category: fe65]]
[[Category: protein binding]]
[[Category: ww domain]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:28:15 2008''
Retrieved from "https://proteopedia.org/2idh"