2ho2

From Proteopedia

(Difference between revisions)

Revision as of 07:18, 24 March 2021

Structure of human FE65-WW domain in complex with hMena peptide.

Structural highlights

2ho2 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	APBB1, FE65 (HUMAN)
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] [ENAH_HUMAN] Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity).^[6] ^[7]

Evolutionary Conservation

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

Publication Abstract from PubMed

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.

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:17686488^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Krugmann S, Jordens I, Gevaert K, Driessens M, Vandekerckhove J, Hall A. Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr Biol. 2001 Oct 30;11(21):1645-55. PMID:11696321
↑ Boeda B, Briggs DC, Higgins T, Garvalov BK, Fadden AJ, McDonald NQ, Way M. Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding. Mol Cell. 2007 Dec 28;28(6):1071-82. PMID:18158903 doi:10.1016/j.molcel.2007.10.033
↑ Meiyappan M, Birrane G, Ladias JA. Structural basis for polyproline recognition by the FE65 WW domain. J Mol Biol. 2007 Sep 28;372(4):970-80. Epub 2007 Jun 29. PMID:17686488 doi:10.1016/j.jmb.2007.06.064

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ho2"

@@ Line 1: / Line 1: @@
 ==Structure of human FE65-WW domain in complex with hMena peptide.==
-<StructureSection load='2ho2' size='340' side='right' caption='[[2ho2]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
+<StructureSection load='2ho2' size='340' side='right'caption='[[2ho2]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ho2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HO2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HO2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ho2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HO2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</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></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APBB1, FE65 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APBB1, FE65 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ho2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ho2 OCA], [http://pdbe.org/2ho2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ho2 RCSB], [http://www.ebi.ac.uk/pdbsum/2ho2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ho2 ProSAT]</span></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=2ho2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ho2 OCA], [https://pdbe.org/2ho2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ho2 RCSB], [https://www.ebi.ac.uk/pdbsum/2ho2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ho2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>  [[http://www.uniprot.org/uniprot/ENAH_HUMAN ENAH_HUMAN]] Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity).<ref>PMID:11696321</ref> <ref>PMID:18158903</ref>
+[[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>  [[https://www.uniprot.org/uniprot/ENAH_HUMAN ENAH_HUMAN]] Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity).<ref>PMID:11696321</ref> <ref>PMID:18158903</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/ho/2ho2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ho/2ho2_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Birrane, G]]
 [[Category: Ladias, J A]]

2ho2

From Proteopedia

Revision as of 07:18, 24 March 2021

Structure of human FE65-WW domain in complex with hMena peptide.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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