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| | ==Structure of inner kinetochore CCAN complex with mask1== | | ==Structure of inner kinetochore CCAN complex with mask1== |
| - | <StructureSection load='6qlf' size='340' side='right'caption='[[6qlf]], [[Resolution|resolution]] 3.45Å' scene=''> | + | <SX load='6qlf' size='340' side='right' viewer='molstar' caption='[[6qlf]], [[Resolution|resolution]] 3.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qlf]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QLF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QLF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qlf]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QLF 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=6qlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qlf OCA], [http://pdbe.org/6qlf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qlf RCSB], [http://www.ebi.ac.uk/pdbsum/6qlf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qlf 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]] 3.45Å</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=6qlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qlf OCA], [https://pdbe.org/6qlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qlf RCSB], [https://www.ebi.ac.uk/pdbsum/6qlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qlf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CENPU_YEAST CENPU_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:14633972</ref> [[http://www.uniprot.org/uniprot/CENPO_YEAST CENPO_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:9987135</ref> [[http://www.uniprot.org/uniprot/NKP1_YEAST NKP1_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:22561346</ref> [[http://www.uniprot.org/uniprot/CENPN_YEAST CENPN_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:9339342</ref> [[http://www.uniprot.org/uniprot/NKP2_YEAST NKP2_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:22561346</ref> [[http://www.uniprot.org/uniprot/CENPL_YEAST CENPL_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:11361335</ref> <ref>PMID:15241623</ref> [[http://www.uniprot.org/uniprot/CENPP_YEAST CENPP_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:10323865</ref> <ref>PMID:14633972</ref> [[http://www.uniprot.org/uniprot/CENPQ_YEAST CENPQ_YEAST]] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:10323865</ref> <ref>PMID:14633972</ref> | + | [https://www.uniprot.org/uniprot/CENPL_YEAST CENPL_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.<ref>PMID:11361335</ref> <ref>PMID:15241623</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | In eukaryotes, accurate chromosome segregation in mitosis and meiosis maintains genome stability and prevents aneuploidy. Kinetochores are large protein complexes that, by assembling onto specialized Cenp-A nucleosomes(1,2), function to connect centromeric chromatin to microtubules of the mitotic spindle(3,4). Whereas the centromeres of vertebrate chromosomes comprise millions of DNA base pairs and attach to multiple microtubules, the simple point centromeres of budding yeast are connected to individual microtubules(5,6). All 16 budding yeast chromosomes assemble complete kinetochores using a single Cenp-A nucleosome (Cenp-A(Nuc)), each of which is perfectly centred on its cognate centromere(7-9). The inner and outer kinetochore modules are responsible for interacting with centromeric chromatin and microtubules, respectively. Here we describe the cryo-electron microscopy structure of the Saccharomyces cerevisiae inner kinetochore module, the constitutive centromere associated network (CCAN) complex, assembled onto a Cenp-A nucleosome (CCAN-Cenp-A(Nuc)). The structure explains the interdependency of the constituent subcomplexes of CCAN and shows how the Y-shaped opening of CCAN accommodates Cenp-A(Nuc) to enable specific CCAN subunits to contact the nucleosomal DNA and histone subunits. Interactions with the unwrapped DNA duplex at the two termini of Cenp-A(Nuc) are mediated predominantly by a DNA-binding groove in the Cenp-L-Cenp-N subcomplex. Disruption of these interactions impairs assembly of CCAN onto Cenp-A(Nuc). Our data indicate a mechanism of Cenp-A nucleosome recognition by CCAN and how CCAN acts as a platform for assembly of the outer kinetochore to link centromeres to the mitotic spindle for chromosome segregation. |
| | + | |
| | + | Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.,Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D Nature. 2019 Oct 2. pii: 10.1038/s41586-019-1609-1. doi:, 10.1038/s41586-019-1609-1. PMID:31578520<ref>PMID:31578520</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6qlf" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Centromere protein 3D structure|Centromere protein 3D structure]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Barford, D]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Chang, L]] | + | [[Category: Barford D]] |
| - | [[Category: Fasci, D]] | + | [[Category: Chang L]] |
| - | [[Category: Heck, A J.R]] | + | [[Category: Fasci D]] |
| - | [[Category: McLaughlin, S H]] | + | [[Category: Heck AJR]] |
| - | [[Category: Yan, K]] | + | [[Category: McLaughlin SH]] |
| - | [[Category: Yang, J]] | + | [[Category: Yan K]] |
| - | [[Category: Zhang, Z]] | + | [[Category: Yang J]] |
| - | [[Category: Ccan]]
| + | [[Category: Zhang Z]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Inner kinetochore]]
| + | |
| Structural highlights
Function
CENPL_YEAST Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[1] [2]
Publication Abstract from PubMed
In eukaryotes, accurate chromosome segregation in mitosis and meiosis maintains genome stability and prevents aneuploidy. Kinetochores are large protein complexes that, by assembling onto specialized Cenp-A nucleosomes(1,2), function to connect centromeric chromatin to microtubules of the mitotic spindle(3,4). Whereas the centromeres of vertebrate chromosomes comprise millions of DNA base pairs and attach to multiple microtubules, the simple point centromeres of budding yeast are connected to individual microtubules(5,6). All 16 budding yeast chromosomes assemble complete kinetochores using a single Cenp-A nucleosome (Cenp-A(Nuc)), each of which is perfectly centred on its cognate centromere(7-9). The inner and outer kinetochore modules are responsible for interacting with centromeric chromatin and microtubules, respectively. Here we describe the cryo-electron microscopy structure of the Saccharomyces cerevisiae inner kinetochore module, the constitutive centromere associated network (CCAN) complex, assembled onto a Cenp-A nucleosome (CCAN-Cenp-A(Nuc)). The structure explains the interdependency of the constituent subcomplexes of CCAN and shows how the Y-shaped opening of CCAN accommodates Cenp-A(Nuc) to enable specific CCAN subunits to contact the nucleosomal DNA and histone subunits. Interactions with the unwrapped DNA duplex at the two termini of Cenp-A(Nuc) are mediated predominantly by a DNA-binding groove in the Cenp-L-Cenp-N subcomplex. Disruption of these interactions impairs assembly of CCAN onto Cenp-A(Nuc). Our data indicate a mechanism of Cenp-A nucleosome recognition by CCAN and how CCAN acts as a platform for assembly of the outer kinetochore to link centromeres to the mitotic spindle for chromosome segregation.
Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.,Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D Nature. 2019 Oct 2. pii: 10.1038/s41586-019-1609-1. doi:, 10.1038/s41586-019-1609-1. PMID:31578520[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ghosh SK, Poddar A, Hajra S, Sanyal K, Sinha P. The IML3/MCM19 gene of Saccharomyces cerevisiae is required for a kinetochore-related process during chromosome segregation. Mol Genet Genomics. 2001 Apr;265(2):249-57. PMID:11361335
- ↑ Ghosh SK, Sau S, Lahiri S, Lohia A, Sinha P. The Iml3 protein of the budding yeast is required for the prevention of precocious sister chromatid separation in meiosis I and for sister chromatid disjunction in meiosis II. Curr Genet. 2004 Aug;46(2):82-91. Epub 2004 Jul 6. PMID:15241623 doi:http://dx.doi.org/10.1007/s00294-004-0516-6
- ↑ Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D. Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. Nature. 2019 Oct 2. pii: 10.1038/s41586-019-1609-1. doi:, 10.1038/s41586-019-1609-1. PMID:31578520 doi:http://dx.doi.org/10.1038/s41586-019-1609-1
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