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6tvm

From Proteopedia

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LEDGF/p75 dimer (residues 345-467)

Structural highlights

6tvm is a 2 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]

Publication Abstract from PubMed

Dimerization of many eukaryotic transcription regulatory factors is critical for their function. Regulatory role of an epigenetic reader lens epithelium-derived growth factor/p75 (LEDGF/p75) requires at least two copies of this protein to overcome the nucleosome-induced barrier to transcription elongation. Moreover, various LEDGF/p75 binding partners are enriched for dimeric features, further underscoring the functional regulatory role of LEDGF/p75 dimerization. Here, we dissected the minimal dimerization region in the C-terminal part of LEDGF/p75 and, using paramagnetic NMR spectroscopy, identified the key molecular contacts that helped to refine the solution structure of the dimer. The LEDGF/p75 dimeric assembly is stabilized by domain swapping within the integrase binding domain and additional electrostatic "stapling" of the negatively charged alpha helix formed in the intrinsically disordered C-terminal region. We validated the dimerization mechanism using structure-inspired dimerization defective LEDGF/p75 variants and chemical crosslinking coupled to mass spectrometry. We also show how dimerization might affect the LEDGF/p75 interactome.

Molecular Mechanism of LEDGF/p75 Dimerization.,Lux V, Brouns T, Cermakova K, Srb P, Fabry M, Madlikova M, Horejsi M, Kukacka Z, Novak P, Kugler M, Brynda J, DeRijck J, Christ F, Debyser Z, Veverka V Structure. 2020 Sep 14. pii: S0969-2126(20)30325-7. doi:, 10.1016/j.str.2020.08.012. PMID:32946742^[2]

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
↑ Lux V, Brouns T, Cermakova K, Srb P, Fabry M, Madlikova M, Horejsi M, Kukacka Z, Novak P, Kugler M, Brynda J, DeRijck J, Christ F, Debyser Z, Veverka V. Molecular Mechanism of LEDGF/p75 Dimerization. Structure. 2020 Sep 14. pii: S0969-2126(20)30325-7. doi:, 10.1016/j.str.2020.08.012. PMID:32946742 doi:http://dx.doi.org/10.1016/j.str.2020.08.012

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/6tvm"

Categories: Homo sapiens | Large Structures | Lux V | Veverka V

@@ Line 1: / Line 1: @@
 ==LEDGF/p75 dimer (residues 345-467)==
-<StructureSection load='6tvm' size='340' side='right'caption='[[6tvm]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''>
+<StructureSection load='6tvm' size='340' side='right'caption='[[6tvm]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6tvm]] is a 2 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=6TVM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TVM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6tvm]] 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=6TVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TVM FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PSIP1, DFS70, LEDGF, PSIP2 ([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=6tvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tvm OCA], [https://pdbe.org/6tvm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tvm RCSB], [https://www.ebi.ac.uk/pdbsum/6tvm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tvm ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tvm OCA], [http://pdbe.org/6tvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tvm RCSB], [http://www.ebi.ac.uk/pdbsum/6tvm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tvm 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lux, V]]
+[[Category: Lux V]]
-[[Category: Veverka, V]]
+[[Category: Veverka V]]
-[[Category: Domain-swapped dimer]]
-[[Category: Epigenetic reader]]
-[[Category: Integrase-binding domain]]
-[[Category: Transcription]]

6tvm

From Proteopedia

Current revision

LEDGF/p75 dimer (residues 345-467)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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