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| | ==Solution structure of the Hs. PSIP1 PWWP domain== | | ==Solution structure of the Hs. PSIP1 PWWP domain== |
| - | <StructureSection load='3zeh' size='340' side='right'caption='[[3zeh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='3zeh' size='340' side='right'caption='[[3zeh]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zeh]] is a 1 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=3ZEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZEH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zeh]] 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=3ZEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZEH FirstGlance]. <br> |
| | </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=3zeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zeh OCA], [https://pdbe.org/3zeh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zeh RCSB], [https://www.ebi.ac.uk/pdbsum/3zeh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zeh ProSAT]</span></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=3zeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zeh OCA], [https://pdbe.org/3zeh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zeh RCSB], [https://www.ebi.ac.uk/pdbsum/3zeh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zeh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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.
| + | [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 == |
| - | [[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/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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Boelens, R]] | + | [[Category: Boelens R]] |
| - | [[Category: Ingen, H van]] | + | [[Category: Timmers HTM]] |
| - | [[Category: Nuland, R van]] | + | [[Category: Van Ingen H]] |
| - | [[Category: Timmers, H T.M]]
| + | [[Category: Van Nuland R]] |
| - | [[Category: Dna binding]] | + | |
| Structural highlights
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
BACKGROUND: Recognition of histone modifications by specialized protein domains is a key step in the regulation of DNA-mediated processes like gene transcription. The structural basis of these interactions is usually studied using histone peptide models, neglecting the nucleosomal context. Here, we provide the structural and thermodynamic basis for the recognition of H3K36-methylated (H3K36me) nucleosomes by the PSIP1-PWWP domain, based on extensive mutational analysis, advanced nuclear magnetic resonance (NMR), and computational approaches. RESULTS: The PSIP1-PWWP domain binds H3K36me3 peptide and DNA with low affinity, through distinct, adjacent binding surfaces. PWWP binding to H3K36me nucleosomes is enhanced approximately 10,000-fold compared to a methylated peptide. Based on mutational analyses and NMR data, we derive a structure of the complex showing that the PWWP domain is bound to H3K36me nucleosomes through simultaneous interactions with both methylated histone tail and nucleosomal DNA. CONCLUSION: Concerted binding to the methylated histone tail and nucleosomal DNA underlies the high- affinity, specific recognition of H3K36me nucleosomes by the PSIP1-PWWP domain. We propose that this bipartite binding mechanism is a distinctive and general property in the recognition of histone modifications close to the nucleosome core.
Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain.,van Nuland R, van Schaik FM, Simonis M, van Heesch S, Cuppen E, Boelens R, Timmers HM, van Ingen H Epigenetics Chromatin. 2013 May 8;6(1):12. doi: 10.1186/1756-8935-6-12. PMID:23656834[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
- ↑ van Nuland R, van Schaik FM, Simonis M, van Heesch S, Cuppen E, Boelens R, Timmers HM, van Ingen H. Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain. Epigenetics Chromatin. 2013 May 8;6(1):12. doi: 10.1186/1756-8935-6-12. PMID:23656834 doi:10.1186/1756-8935-6-12
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