2n3a

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==Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404)==
==Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404)==
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<StructureSection load='2n3a' size='340' side='right'caption='[[2n3a]], [[NMR_Ensembles_of_Models | 29 NMR models]]' scene=''>
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<StructureSection load='2n3a' size='340' side='right'caption='[[2n3a]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2n3a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N3A FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2n3a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N3A FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PSIP1, DFS70, LEDGF, PSIP2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2n3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3a OCA], [https://pdbe.org/2n3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n3a RCSB], [https://www.ebi.ac.uk/pdbsum/2n3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3a 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=2n3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3a OCA], [https://pdbe.org/2n3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n3a RCSB], [https://www.ebi.ac.uk/pdbsum/2n3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3a ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN]] Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4.
 
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/POGZ_HUMAN POGZ_HUMAN]] Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms.<ref>PMID:20562864</ref> [[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN]] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.<ref>PMID:15642333</ref>
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[https://www.uniprot.org/uniprot/POGZ_HUMAN POGZ_HUMAN] Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms.<ref>PMID:20562864</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Lens epithelium-derived growth factor (LEDGF/p75) is an epigenetic reader and attractive therapeutic target involved in HIV integration and the development of mixed lineage leukaemia (MLL1) fusion-driven leukaemia. Besides HIV integrase and the MLL1-menin complex, LEDGF/p75 interacts with various cellular proteins via its integrase binding domain (IBD). Here we present structural characterization of IBD interactions with transcriptional repressor JPO2 and domesticated transposase PogZ, and show that the PogZ interaction is nearly identical to the interaction of LEDGF/p75 with MLL1. The interaction with the IBD is maintained by an intrinsically disordered IBD-binding motif (IBM) common to all known cellular partners of LEDGF/p75. In addition, based on IBM conservation, we identify and validate IWS1 as a novel LEDGF/p75 interaction partner. Our results also reveal how HIV integrase efficiently displaces cellular binding partners from LEDGF/p75. Finally, the similar binding modes of LEDGF/p75 interaction partners represent a new challenge for the development of selective interaction inhibitors.
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Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif.,Tesina P, Cermakova K, Horejsi M, Prochazkova K, Fabry M, Sharma S, Christ F, Demeulemeester J, Debyser Z, Rijck JD, Veverka V, Rezacova P Nat Commun. 2015 Aug 6;6:7968. doi: 10.1038/ncomms8968. PMID:26245978<ref>PMID:26245978</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2n3a" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Cermakova, K]]
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[[Category: Cermakova K]]
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[[Category: Christ, F]]
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[[Category: Christ F]]
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[[Category: Debyser, Z]]
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[[Category: De Rijck J]]
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[[Category: Demeulemeester, J]]
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[[Category: Debyser Z]]
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[[Category: Fabry, M]]
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[[Category: Demeulemeester J]]
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[[Category: Horejsi, M]]
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[[Category: Fabry M]]
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[[Category: Prochazkova, K]]
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[[Category: Horejsi M]]
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[[Category: Rezacova, P]]
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[[Category: Prochazkova K]]
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[[Category: Rijck, J De]]
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[[Category: Rezacova P]]
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[[Category: Sharma, S]]
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[[Category: Sharma S]]
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[[Category: Tesina, P]]
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[[Category: Tesina P]]
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[[Category: Veverka, V]]
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[[Category: Veverka V]]
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[[Category: H3k36me3]]
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[[Category: Ledgf/p75]]
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[[Category: Pogz]]
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[[Category: Protein binding]]
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Current revision

Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404)

PDB ID 2n3a

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