6emp

From Proteopedia

(Difference between revisions)

Revision as of 10:43, 14 June 2023

Solution structure of the LEDGF/p75 IBD - POGZ (aa 1370-1404) complex

Structural highlights

6emp is a 1 chain structure with sequence from Homo sapiens. 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

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.^[1] 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.^[2]

Publication Abstract from PubMed

Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.

Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.,Sharma S, Cermakova K, De Rijck J, Demeulemeester J, Fabry M, El Ashkar S, Van Belle S, Lepsik M, Tesina P, Duchoslav V, Novak P, Hubalek M, Srb P, Christ F, Rezacova P, Hodges HC, Debyser Z, Veverka V Proc Natl Acad Sci U S A. 2018 Jul 11. pii: 1803909115. doi:, 10.1073/pnas.1803909115. PMID:29997176^[3]

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

References

↑ 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
↑ 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
↑ Sharma S, Cermakova K, De Rijck J, Demeulemeester J, Fabry M, El Ashkar S, Van Belle S, Lepsik M, Tesina P, Duchoslav V, Novak P, Hubalek M, Srb P, Christ F, Rezacova P, Hodges HC, Debyser Z, Veverka V. Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation. Proc Natl Acad Sci U S A. 2018 Jul 11. pii: 1803909115. doi:, 10.1073/pnas.1803909115. PMID:29997176 doi:http://dx.doi.org/10.1073/pnas.1803909115

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/6emp"

Categories: Homo sapiens | Large Structures | Veverka V

@@ Line 1: / Line 1: @@
 ==Solution structure of the LEDGF/p75 IBD - POGZ (aa 1370-1404) complex==
-<StructureSection load='6emp' size='340' side='right'caption='[[6emp]], [[NMR_Ensembles_of_Models | 40 NMR models]]' scene=''>
+<StructureSection load='6emp' size='340' side='right'caption='[[6emp]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6emp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EMP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6emp]] is a 1 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=6EMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EMP FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POGZ, KIAA0461, SUHW5, ZNF280E, ZNF635, Nbla00003 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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=6emp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6emp OCA], [https://pdbe.org/6emp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6emp RCSB], [https://www.ebi.ac.uk/pdbsum/6emp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6emp ProSAT]</span></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=6emp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6emp OCA], [http://pdbe.org/6emp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6emp RCSB], [http://www.ebi.ac.uk/pdbsum/6emp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6emp ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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.
+[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 ==
-[[http://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>
+[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> [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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Veverka, V]]
+[[Category: Veverka V]]
-[[Category: Epigenetic]]
-[[Category: Leukemia]]
-[[Category: Protein-protein complex]]
-[[Category: Transcription]]

6emp

From Proteopedia

Revision as of 10:43, 14 June 2023

Solution structure of the LEDGF/p75 IBD - POGZ (aa 1370-1404) complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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