6QLD

Structure of inner kinetochore CCAN-Cenp-A complex

Summary for 6QLD

• Entry DOI: 10.2210/pdb6qld/pdb
• EMDB information: 4579
• Descriptor: Inner kinetochore subunit MIF2, Inner kinetochore subunit CTF19, Inner kinetochore subunit OKP1, ... (21 entities in total)
• Functional Keywords: inner kinetochore, dna, nucleosome, dna binding protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 22
• Total formula weight: 471670.06

Authors

Yan, K.,Yang, J.,Zhang, Z.,McLaughlin, S.H.,Chang, L.,Fasci, D.,Heck, A.J.R.,Barford, D. (deposition date: 2019-01-31, release date: 2019-10-02, Last modification date: 2024-05-15)

Primary citation

Yan, K.,Yang, J.,Zhang, Z.,McLaughlin, S.H.,Chang, L.,Fasci, D.,Ehrenhofer-Murray, A.E.,Heck, A.J.R.,Barford, D.
Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.
Nature, 574:278-282, 2019

PubMed Abstract: 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, function to connect centromeric chromatin to microtubules of the mitotic spindle. 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. All 16 budding yeast chromosomes assemble complete kinetochores using a single Cenp-A nucleosome (Cenp-A), each of which is perfectly centred on its cognate centromere. 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). The structure explains the interdependency of the constituent subcomplexes of CCAN and shows how the Y-shaped opening of CCAN accommodates Cenp-A 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 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. 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.

PubMed: 31578520
DOI: 10.1038/s41586-019-1609-1

Experimental method

ELECTRON MICROSCOPY (4.15 Å)