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2n3a

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Revision as of 14:13, 24 May 2017

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

Structural highlights

2n3a is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.^[1] [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.^[2]

Publication Abstract from PubMed

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.

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^[3]

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

References

↑ Nozawa RS, Nagao K, Masuda HT, Iwasaki O, Hirota T, Nozaki N, Kimura H, Obuse C. Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation. Nat Cell Biol. 2010 Jul;12(7):719-27. doi: 10.1038/ncb2075. Epub 2010 Jun 20. PMID:20562864 doi:http://dx.doi.org/10.1038/ncb2075
↑ Chylack LT Jr, Fu L, Mancini R, Martin-Rehrmann MD, Saunders AJ, Konopka G, Tian D, Hedley-Whyte ET, Folkerth RD, Goldstein LE. Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain. Exp Eye Res. 2004 Dec;79(6):941-8. PMID:15642333 doi:S0014-4835(04)00250-7
↑ Tesina P, Cermakova K, Horejsi M, Prochazkova K, Fabry M, Sharma S, Christ F, Demeulemeester J, Debyser Z, Rijck JD, Veverka V, Rezacova P. Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif. Nat Commun. 2015 Aug 6;6:7968. doi: 10.1038/ncomms8968. PMID:26245978 doi:http://dx.doi.org/10.1038/ncomms8968

1 Structural highlights
2 Disease
3 Function
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/2n3a"

@@ Line 1: / Line 1: @@
 ==Solution structure of LEDGF/p75 IBD in complex with POGZ peptide (1389-1404)==
 <StructureSection load='2n3a' size='340' side='right' caption='[[2n3a]], [[NMR_Ensembles_of_Models | 29 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2n3a]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N3A FirstGlance]. <br>
-</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=2n3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2n3a RCSB], [http://www.ebi.ac.uk/pdbsum/2n3a PDBsum]</span></td></tr>
+</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=2n3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3a OCA], [http://pdbe.org/2n3a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n3a RCSB], [http://www.ebi.ac.uk/pdbsum/2n3a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3a ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2n3a" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2n3a

From Proteopedia

Revision as of 14:13, 24 May 2017

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

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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