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| | <SX load='6pwx' size='340' side='right' viewer='molstar' caption='[[6pwx]], [[Resolution|resolution]] 4.20Å' scene=''> | | <SX load='6pwx' size='340' side='right' viewer='molstar' caption='[[6pwx]], [[Resolution|resolution]] 4.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pwx]] is a 11 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PWX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pwx]] is a 11 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=6PWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PWX FirstGlance]. <br> |
| - | </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=6pwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pwx OCA], [http://pdbe.org/6pwx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pwx RCSB], [http://www.ebi.ac.uk/pdbsum/6pwx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pwx ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2Å</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=6pwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pwx OCA], [https://pdbe.org/6pwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pwx RCSB], [https://www.ebi.ac.uk/pdbsum/6pwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pwx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/H2A1_XENLA H2A1_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. [[http://www.uniprot.org/uniprot/RBBP5_HUMAN RBBP5_HUMAN]] In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.<ref>PMID:19556245</ref> [[http://www.uniprot.org/uniprot/H4_XENLA 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. [[http://www.uniprot.org/uniprot/H32_XENLA H32_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. [[http://www.uniprot.org/uniprot/H2B11_XENLA 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. | + | [https://www.uniprot.org/uniprot/RBBP5_HUMAN RBBP5_HUMAN] In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.<ref>PMID:19556245</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1(SET) domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.
| + | |
| | | | |
| - | Cryo-EM structure of the human MLL1 core complex bound to the nucleosome.,Park SH, Ayoub A, Lee YT, Xu J, Kim H, Zheng W, Zhang B, Sha L, An S, Zhang Y, Cianfrocco MA, Su M, Dou Y, Cho US Nat Commun. 2019 Dec 5;10(1):5540. doi: 10.1038/s41467-019-13550-2. PMID:31804488<ref>PMID:31804488</ref>
| + | ==See Also== |
| - | | + | *[[Histone 3D structures|Histone 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | *[[Retinoblastoma-binding protein 3D structures|Retinoblastoma-binding protein 3D structures]] |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6pwx" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ayoub, A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Cho, U]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Cianfrocco, M A]] | + | [[Category: Ayoub A]] |
| - | [[Category: Dou, Y]] | + | [[Category: Cho U]] |
| - | [[Category: Lee, Y T]] | + | [[Category: Cianfrocco MA]] |
| - | [[Category: Park, S H]] | + | [[Category: Dou Y]] |
| - | [[Category: Su, M]] | + | [[Category: Lee YT]] |
| - | [[Category: Xu, J]] | + | [[Category: Park SH]] |
| - | [[Category: Zhang, B]] | + | [[Category: Su M]] |
| - | [[Category: Zhang, W]] | + | [[Category: Xu J]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang B]] |
| - | [[Category: Ash2l]]
| + | [[Category: Zhang W]] |
| - | [[Category: Dpy30]]
| + | [[Category: Zhang Y]] |
| - | [[Category: Histone binding-dna binding-dna complex]]
| + | |
| - | [[Category: Histone h3 lys4 methyltransferase]]
| + | |
| - | [[Category: Mixed-lineage leukemia]]
| + | |
| - | [[Category: Mll1]]
| + | |
| - | [[Category: Nucleosome]]
| + | |
| - | [[Category: Rbbp5]]
| + | |
| - | [[Category: Wdr5]]
| + | |
