6QLE

Structure of inner kinetochore CCAN complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.55 Å
  • Resolution: 3.55 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.

Yan, K.Yang, J.Zhang, Z.McLaughlin, S.H.Chang, L.Fasci, D.Ehrenhofer-Murray, A.E.Heck, A.J.R.Barford, D.

(2019) Nature 574: 278-282

  • DOI: https://doi.org/10.1038/s41586-019-1609-1
  • Primary Citation of Related Structures:  
    6QLD, 6QLE, 6QLF

  • 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 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.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Cambridge, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Central kinetochore subunit MCM16,Central kinetochore subunit MCM16,Inner kinetochore subunit MCM16,Mcm16pA [auth H]181Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: SCRG_02534FOSTERSB_4937
UniProt
Find proteins for Q12262 (Saccharomyces cerevisiae (strain ATCC 204508 / S288c))
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Central kinetochore subunit CTF3,Inner kinetochore subunit CTF3,Central kinetochore subunit CTF3,Inner kinetochore subunit CTF3B [auth I]412Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: SCRG_04321
UniProt
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit MCM22,Inner kinetochore subunit MCM22,Inner kinetochore subunit MCM22,Inner kinetochore subunit MCM22C [auth K]204Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: MCM22YJR135CJ2122
UniProt
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit IML3D [auth L]245Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: IML3MCM19YBR107CYBR0836
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit CHL4E [auth N]458Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: CHL4CTF17MCM17YDR254WYD9320A.04
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit MCM21F [auth O]368Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: MCM21CTF5YDR318W
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit CTF19G [auth P]369Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: CTF19MCM18YPL018WLPB13W
UniProt
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit OKP1,Inner kinetochore subunit OKP1,Inner kinetochore subunit OKP1,Inner kinetochore subunit OKP1H [auth Q]261Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: OKP1YGR179C
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit AME1,Inner kinetochore subunit AME1,Inner kinetochore subunit AME1,Inner kinetochore subunit AME1I [auth U]186Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: AME1ARP100YBR211CYBR1458
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit NKP1J [auth Y]238Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: NKP1YDR383C
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
Inner kinetochore subunit NKP2K [auth Z]153Saccharomyces cerevisiaeMutation(s): 0 
Gene Names: NKP2YLR315W
UniProt
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.55 Å
  • Resolution: 3.55 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomMC_UP_1201/6
Cancer Research UKUnited KingdomC576/A14109
European CommissionHorizon 2020 program INFRAIA project Epic-XS (Project 823839)

Revision History  (Full details and data files)

  • Version 1.0: 2019-10-02
    Type: Initial release
  • Version 1.1: 2019-10-16
    Changes: Data collection, Database references
  • Version 1.2: 2019-11-27
    Changes: Database references