8du4: Difference between revisions
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==Complex between RbBP5-WDR5 and an H2B-ubiquitinated nucleosome== | |||
<StructureSection load='8du4' size='340' side='right'caption='[[8du4]], [[Resolution|resolution]] 3.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8du4]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DU4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.55Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></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=8du4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8du4 OCA], [https://pdbe.org/8du4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8du4 RCSB], [https://www.ebi.ac.uk/pdbsum/8du4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8du4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/H3C_XENLA H3C_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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, WDR5, RbBp5, Ash2L, and DPY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex. | |||
Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome.,Rahman S, Hoffmann NA, Worden EJ, Smith ML, Namitz KEW, Knutson BA, Cosgrove MS, Wolberger C Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2205691119. doi: , 10.1073/pnas.2205691119. Epub 2022 Sep 12. PMID:36095189<ref>PMID:36095189</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8du4" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Rahman | ==See Also== | ||
[[Category: Worden | *[[Histone 3D structures|Histone 3D structures]] | ||
*[[Retinoblastoma-binding protein 3D structures|Retinoblastoma-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Xenopus laevis]] | |||
[[Category: Niklas HA]] | |||
[[Category: Rahman S]] | |||
[[Category: Wolberger C]] | |||
[[Category: Worden EJ]] | |||
Latest revision as of 15:03, 23 October 2024
Complex between RbBP5-WDR5 and an H2B-ubiquitinated nucleosomeComplex between RbBP5-WDR5 and an H2B-ubiquitinated nucleosome
Structural highlights
FunctionH3C_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 PubMedThe human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, WDR5, RbBp5, Ash2L, and DPY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex. Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome.,Rahman S, Hoffmann NA, Worden EJ, Smith ML, Namitz KEW, Knutson BA, Cosgrove MS, Wolberger C Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2205691119. doi: , 10.1073/pnas.2205691119. Epub 2022 Sep 12. PMID:36095189[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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