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6s01

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Structure of LEDGF PWWP domain bound H3K36 methylated nucleosome

6s01, resolution 3.20Å

Structural highlights

6s01 is a 11 chain structure with sequence from African clawed frog and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	XELAEV_18002543mg (African clawed frog), hist1h2aj, LOC494591, XELAEV_18003602mg (African clawed frog), PSIP1, DFS70, LEDGF, PSIP2 (HUMAN)
Experimental data:	Check to display Experimental Data
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

[H2B11_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [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] [H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Publication Abstract from PubMed

Recognition of histone-modified nucleosomes by specific reader domains underlies the regulation of chromatin-associated processes. Whereas structural studies revealed how reader domains bind modified histone peptides, it is unclear how reader domains interact with modified nucleosomes. Here, we report the cryo-electron microscopy structure of the PWWP reader domain of human transcriptional coactivator LEDGF in complex with an H3K36-methylated nucleosome at 3.2-A resolution. The structure reveals multivalent binding of the reader domain to the methylated histone tail and to both gyres of nucleosomal DNA, explaining the known cooperative interactions. The observed cross-gyre binding may contribute to nucleosome integrity during transcription. The structure also explains how human PWWP domain-containing proteins are recruited to H3K36-methylated regions of the genome for transcription, histone acetylation and methylation, and for DNA methylation and repair.

Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding.,Wang H, Farnung L, Dienemann C, Cramer P Nat Struct Mol Biol. 2019 Dec 9. pii: 10.1038/s41594-019-0345-4. doi:, 10.1038/s41594-019-0345-4. PMID:31819277^[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
↑ Wang H, Farnung L, Dienemann C, Cramer P. Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding. Nat Struct Mol Biol. 2019 Dec 9. pii: 10.1038/s41594-019-0345-4. doi:, 10.1038/s41594-019-0345-4. PMID:31819277 doi:http://dx.doi.org/10.1038/s41594-019-0345-4

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/6s01"

@@ Line 3: / Line 3: @@
 <SX load='6s01' size='340' side='right' viewer='molstar' caption='[[6s01]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6s01]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S01 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S01 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6s01]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S01 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6S01 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ML3:2-{[(2R)-2-AMINO-2-CARBOXYETHYL]SULFANYL}-N,N,N-TRIMETHYLETHANAMINIUM'>ML3</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">XELAEV_18002543mg ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), hist1h2aj, LOC494591, XELAEV_18003602mg ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), PSIP1, DFS70, LEDGF, PSIP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6s01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s01 OCA], [http://pdbe.org/6s01 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s01 RCSB], [http://www.ebi.ac.uk/pdbsum/6s01 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s01 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=6s01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s01 OCA], [http://pdbe.org/6s01 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s01 RCSB], [http://www.ebi.ac.uk/pdbsum/6s01 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s01 ProSAT]</span></td></tr>
 </table>
 == Disease ==

6s01

From Proteopedia

Current revision

Structure of LEDGF PWWP domain bound H3K36 methylated nucleosome

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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