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| | ==Crystal structure of the nucleosome containing a chimeric histone H3/CENP-A CATD== | | ==Crystal structure of the nucleosome containing a chimeric histone H3/CENP-A CATD== |
| - | <StructureSection load='5z23' size='340' side='right' caption='[[5z23]], [[Resolution|resolution]] 2.73Å' scene=''> | + | <StructureSection load='5z23' size='340' side='right'caption='[[5z23]], [[Resolution|resolution]] 2.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5z23]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z23 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z23 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5z23]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z23 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.73Å</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=5z23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z23 OCA], [http://pdbe.org/5z23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z23 RCSB], [http://www.ebi.ac.uk/pdbsum/5z23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z23 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=5z23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z23 OCA], [https://pdbe.org/5z23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z23 RCSB], [https://www.ebi.ac.uk/pdbsum/5z23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z23 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/H2B1J_HUMAN H2B1J_HUMAN]] 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.<ref>PMID:11859126</ref> <ref>PMID:12860195</ref> <ref>PMID:15019208</ref> Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.<ref>PMID:11859126</ref> <ref>PMID:12860195</ref> <ref>PMID:15019208</ref> | + | [https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] [https://www.uniprot.org/uniprot/CENPA_HUMAN CENPA_HUMAN] Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).<ref>PMID:20739937</ref> <ref>PMID:21478274</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: Arimura, Y]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Tachiwana, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Takagi, H]] | + | [[Category: Arimura Y]] |
| - | [[Category: Cenp-a]] | + | [[Category: Tachiwana H]] |
| - | [[Category: Centromere]] | + | [[Category: Takagi H]] |
| - | [[Category: Chromosome]]
| + | |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Dna binding protein-dna complex]]
| + | |
| - | [[Category: Nucleosome]]
| + | |
| Structural highlights
Function
H31_HUMAN CENPA_HUMAN Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).[1] [2]
Publication Abstract from PubMed
Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1(CATD), which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1(CATD) nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes.
The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism.,Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H Nat Commun. 2019 Feb 4;10(1):576. doi: 10.1038/s41467-019-08314-x. PMID:30718488[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Aug 25. PMID:20739937 doi:10.1038/nature09323
- ↑ Hu H, Liu Y, Wang M, Fang J, Huang H, Yang N, Li Y, Wang J, Yao X, Shi Y, Li G, Xu RM. Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP. Genes Dev. 2011 May 1;25(9):901-6. Epub 2011 Apr 8. PMID:21478274 doi:10.1101/gad.2045111
- ↑ Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H. The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism. Nat Commun. 2019 Feb 4;10(1):576. doi: 10.1038/s41467-019-08314-x. PMID:30718488 doi:http://dx.doi.org/10.1038/s41467-019-08314-x
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