3dxe: Difference between revisions

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[[Image:3dxe.png|left|200px]]


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==Crystal structure of the intracellular domain of human APP (T668A mutant) in complex with Fe65-PTB2==
The line below this paragraph, containing "STRUCTURE_3dxe", creates the "Structure Box" on the page.
<StructureSection load='3dxe' size='340' side='right'caption='[[3dxe]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3dxe]] 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=3DXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DXE FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</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&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dxe OCA], [https://pdbe.org/3dxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dxe RCSB], [https://www.ebi.ac.uk/pdbsum/3dxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dxe ProSAT]</span></td></tr>
{{STRUCTURE_3dxe| PDB=3dxe |  SCENE= }}
</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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dx/3dxe_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3dxe ConSurf].
<div style="clear:both"></div>


===Crystal structure of the intracellular domain of human APP (T668A mutant) in complex with Fe65-PTB2===
==See Also==
 
*[[Amyloid precursor protein 3D structures|Amyloid precursor protein 3D structures]]
 
== References ==
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{{ABSTRACT_PUBMED_18833287}}
 
==About this Structure==
3DXE is a 4 chains structure of sequences 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=3DXE OCA].
 
==Reference==
Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2., Radzimanowski J, Simon B, Sattler M, Beyreuther K, Sinning I, Wild K, EMBO Rep. 2008 Nov;9(11):1134-40. Epub 2008 Oct 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18833287 18833287]
 
Overproduction, purification, crystallization and preliminary X-ray analysis of human Fe65-PTB2 in complex with the amyloid precursor protein intracellular domain., Radzimanowski J, Beyreuther K, Sinning I, Wild K, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 May 1;64(Pt, 5):409-12. Epub 2008 Apr 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18453713 18453713]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Radzimanowski, J.]]
[[Category: Large Structures]]
[[Category: Sinning, I.]]
[[Category: Radzimanowski J]]
[[Category: Wild, K.]]
[[Category: Sinning I]]
[[Category: Aicd]]
[[Category: Wild K]]
[[Category: Alternative splicing]]
[[Category: Alzheimer disease]]
[[Category: Alzheimer's disease]]
[[Category: Amyloid]]
[[Category: Apoptosis]]
[[Category: App]]
[[Category: Cell adhesion]]
[[Category: Coated pit]]
[[Category: Copper]]
[[Category: Disease mutation]]
[[Category: Endocytosis]]
[[Category: Fe65]]
[[Category: Glycoprotein]]
[[Category: Heparin-binding]]
[[Category: Iron]]
[[Category: Membrane]]
[[Category: Metal-binding]]
[[Category: Notch signaling pathway]]
[[Category: Phosphoprotein]]
[[Category: Polymorphism]]
[[Category: Protease inhibitor]]
[[Category: Protein binding]]
[[Category: Proteoglycan]]
[[Category: Ptb domain]]
[[Category: Serine protease inhibitor]]
[[Category: Transmembrane]]
[[Category: Zinc]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 19 19:50:47 2008''

Latest revision as of 12:43, 21 February 2024

Crystal structure of the intracellular domain of human APP (T668A mutant) in complex with Fe65-PTB2Crystal structure of the intracellular domain of human APP (T668A mutant) in complex with Fe65-PTB2

Structural highlights

3dxe is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3] [4] [5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. Perkinton MS, Standen CL, Lau KF, Kesavapany S, Byers HL, Ward M, McLoughlin DM, Miller CC. The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling. J Biol Chem. 2004 May 21;279(21):22084-91. Epub 2004 Mar 18. PMID:15031292 doi:10.1074/jbc.M311479200
  2. Nakaya T, Kawai T, Suzuki T. Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells. J Biol Chem. 2008 Jul 4;283(27):19119-31. Epub 2008 May 9. PMID:18468999 doi:M801827200
  3. Lau KF, Chan WM, Perkinton MS, Tudor EL, Chang RC, Chan HY, McLoughlin DM, Miller CC. Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription. J Biol Chem. 2008 Dec 12;283(50):34728-37. Epub 2008 Oct 15. PMID:18922798 doi:M801874200
  4. Cook PJ, Ju BG, Telese F, Wang X, Glass CK, Rosenfeld MG. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature. 2009 Apr 2;458(7238):591-6. doi: 10.1038/nature07849. Epub 2009 Feb 22. PMID:19234442 doi:10.1038/nature07849
  5. Kajiwara Y, Akram A, Katsel P, Haroutunian V, Schmeidler J, Beecham G, Haines JL, Pericak-Vance MA, Buxbaum JD. FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4. PLoS One. 2009;4(4):e5071. doi: 10.1371/journal.pone.0005071. Epub 2009 Apr 3. PMID:19343227 doi:10.1371/journal.pone.0005071

3dxe, resolution 2.00Å

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