6mup

From Proteopedia

(Difference between revisions)

Revision as of 02:56, 11 April 2020

CENP-A nucleosome bound by two copies of CENP-C(CD) and two copies CENP-N(NT)

6mup, resolution 3.50Å

Structural highlights

6mup is a 14 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	6muo
Gene:	CENPA (HUMAN), HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, H4FE, HIST1H4K, H4/D, H4FD, HIST1H4L, H4/K, H4FK, HIST2H4A, H4/N, H4F2, H4FN, HIST2H4, HIST2H4B, H4/O, H4FO, HIST4H4 (HUMAN), HIST1H2AC, H2AFL (HUMAN), HIST2H2BF (HUMAN), CENPN, C16orf60, ICEN32, BM-309 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[H2A1C_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. [CENPC_HUMAN] Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions.^[1] ^[2] [CENPN_HUMAN] Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.^[3] ^[4] ^[5] ^[6] [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).^[7] ^[8] [H2B2F_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.

Publication Abstract from PubMed

Centromeric nucleosomes are at the interface of the chromosome and the kinetochore that connects to spindle microtubules in mitosis. The core centromeric nucleosome complex (CCNC) harbors the histone H3 variant, CENP-A, and its binding proteins, CENP-C (through its central domain; CD) and CENP-N (through its N-terminal domain; NT). CENP-C can engage nucleosomes through two domains: the CD and the CENP-C motif (CM). CENP-C(CD) is part of the CCNC by virtue of its high specificity for CENP-A nucleosomes and ability to stabilize CENP-A at the centromere. CENP-C(CM) is thought to engage a neighboring nucleosome, either one containing conventional H3 or CENP-A, and a crystal structure of a nucleosome complex containing two copies of CENP-C(CM) was reported. Recent structures containing a single copy of CENP-N(NT) bound to the CENP-A nucleosome in the absence of CENP-C were reported. Here, we find that one copy of CENP-N is lost for every two copies of CENP-C on centromeric chromatin just prior to kinetochore formation. We present the structures of symmetric and asymmetric forms of the CCNC that vary in CENP-N stoichiometry. Our structures explain how the central domain of CENP-C achieves its high specificity for CENP-A nucleosomes and how CENP-C and CENP-N sandwich the histone H4 tail. The natural centromeric DNA path in our structures corresponds to symmetric surfaces for CCNC assembly, deviating from what is observed in prior structures using artificial sequences. At mitosis, we propose that CCNC asymmetry accommodates its asymmetric connections at the chromosome/kinetochore interface. VIDEO ABSTRACT.

Structure of the Human Core Centromeric Nucleosome Complex.,Allu PK, Dawicki-McKenna JM, Van Eeuwen T, Slavin M, Braitbard M, Xu C, Kalisman N, Murakami K, Black BE Curr Biol. 2019 Jul 8. pii: S0960-9822(19)30789-4. doi:, 10.1016/j.cub.2019.06.062. PMID:31353180^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gopalakrishnan S, Sullivan BA, Trazzi S, Della Valle G, Robertson KD. DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet. 2009 Sep 1;18(17):3178-93. doi: 10.1093/hmg/ddp256. Epub 2009 May , 29. PMID:19482874 doi:http://dx.doi.org/10.1093/hmg/ddp256
↑ Gascoigne KE, Takeuchi K, Suzuki A, Hori T, Fukagawa T, Cheeseman IM. Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes. Cell. 2011 Apr 29;145(3):410-22. doi: 10.1016/j.cell.2011.03.031. PMID:21529714 doi:http://dx.doi.org/10.1016/j.cell.2011.03.031
↑ Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR 3rd, Cleveland DW. The human CENP-A centromeric nucleosome-associated complex. Nat Cell Biol. 2006 May;8(5):458-69. Epub 2006 Apr 16. PMID:16622419 doi:http://dx.doi.org/ncb1397
↑ Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N, Obuse C, Kisu Y, Goshima N, Nomura F, Nomura N, Yoda K. Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells. Genes Cells. 2006 Jun;11(6):673-84. PMID:16716197 doi:http://dx.doi.org/GTC969
↑ McClelland SE, Borusu S, Amaro AC, Winter JR, Belwal M, McAinsh AD, Meraldi P. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. EMBO J. 2007 Dec 12;26(24):5033-47. doi: 10.1038/sj.emboj.7601927. Epub 2007 Nov , 15. PMID:18007590 doi:http://dx.doi.org/10.1038/sj.emboj.7601927
↑ Carroll CW, Silva MC, Godek KM, Jansen LE, Straight AF. Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N. Nat Cell Biol. 2009 Jul;11(7):896-902. doi: 10.1038/ncb1899. Epub 2009 Jun 21. PMID:19543270 doi:http://dx.doi.org/10.1038/ncb1899
↑ 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
↑ Allu PK, Dawicki-McKenna JM, Van Eeuwen T, Slavin M, Braitbard M, Xu C, Kalisman N, Murakami K, Black BE. Structure of the Human Core Centromeric Nucleosome Complex. Curr Biol. 2019 Jul 8. pii: S0960-9822(19)30789-4. doi:, 10.1016/j.cub.2019.06.062. PMID:31353180 doi:http://dx.doi.org/10.1016/j.cub.2019.06.062

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6mup"

@@ Line 3: / Line 3: @@
 <SX load='6mup' size='340' side='right' viewer='molstar' caption='[[6mup]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mup]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MUP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MUP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mup]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MUP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MUP FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6muo|6muo]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CENPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, H4FE, HIST1H4K, H4/D, H4FD, HIST1H4L, H4/K, H4FK, HIST2H4A, H4/N, H4F2, H4FN, HIST2H4, HIST2H4B, H4/O, H4FO, HIST4H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HIST1H2AC, H2AFL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HIST2H2BF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CENPN, C16orf60, ICEN32, BM-309 ([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=6mup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mup OCA], [http://pdbe.org/6mup PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mup RCSB], [http://www.ebi.ac.uk/pdbsum/6mup PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mup 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=6mup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mup OCA], [http://pdbe.org/6mup PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mup RCSB], [http://www.ebi.ac.uk/pdbsum/6mup PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mup ProSAT]</span></td></tr>
 </table>
 == Function ==

6mup

From Proteopedia

Revision as of 02:56, 11 April 2020

CENP-A nucleosome bound by two copies of CENP-C(CD) and two copies CENP-N(NT)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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