6qld is a 22 chain structure with sequence from [1] and Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[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.[1][2] [H2A1_YEAST] Core component of nucleosome which plays a central role in DNA double strand break (DSB) repair. 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.[3][4][5][6] [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.[7][8] [H2B2_YEAST] 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.[9][10][11][12][13][14][15] [CENPC_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 (PubMed:8408221, PubMed:7579695, PubMed:22561346).[16][17][18] [CENPA_YEAST] 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. Required for functional chromatin architecture at the yeast 2-micron circle partitioning locus and promotes equal plasmid segregation.[19][20][21][22][23][24][25][26][27][28][29] [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.[30] [CENPK_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.[31] [CENPH_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.[32] [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.[33] [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.[34] [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.[35] [H2B1_YEAST] 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.[36][37][38][39][40][41][42][43][44] [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.[45] [CENPI_YEAST] Component of the central kinetochore, which mediates the attachment of the centromere to the mitotic spindle by forming essential interactions between the microtubule-associated outer kinetochore proteins and the centromere-associated inner kinetochore proteins. Required for establishing bipolar spindle-microtubule attachments and proper chromosome segregation. 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.[46] [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.[47][48]
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[49]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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↑ Ortiz J, Stemmann O, Rank S, Lechner J. A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore. Genes Dev. 1999 May 1;13(9):1140-55. PMID:10323865
↑ De Wulf P, McAinsh AD, Sorger PK. Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes. Genes Dev. 2003 Dec 1;17(23):2902-21. Epub 2003 Nov 21. PMID:14633972 doi:http://dx.doi.org/10.1101/gad.1144403
↑ 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
