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TitleModels for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays.
Journal, issue, pagesNat Commun, Year 2026
Publish dateMay 12, 2026
AuthorsCong Yu / Kyle W Muir / Jing Yang / Ziguo Zhang / Stephen H McLaughlin / David Barford /
PubMed AbstractHuman kinetochores assemble onto centromeric DNA comprising repetitive arrays of the 171 bp α-satellite sequence. To understand the higher-order architecture of the inner kinetochore assembled ...Human kinetochores assemble onto centromeric DNA comprising repetitive arrays of the 171 bp α-satellite sequence. To understand the higher-order architecture of the inner kinetochore assembled onto α-satellite arrays, we show cryo-EM structures of CCAN with free DNA, and α-satellite repeat monomers and dimers with CENP-A nucleosomes. CCAN bound to free DNA and a monomeric CENP-A nucleosome engages 70 bp of DNA comprising 30 bp of an upstream α-satellite repeat. This upstream DNA interacts with the histone-fold domain subunits of the CENP-TWSX module in a manner resembling how nucleosomes wrap DNA gyres. A complex of CCAN assembled onto a dimeric α-satellite repeat with two CENP-A nucleosomes shows that CCAN can only be accommodated on the linker DNA by unwrapping DNA from both the CENP-TWSX module and the upstream nucleosome. We discuss the implications of these results for models of CCAN assembly on arrays of α-satellite chromatin containing CENP-A nucleosomes.
External linksNat Commun / PubMed:42120391
MethodsEM (single particle)
Resolution2.7 - 15.5 Å
Structure data

EMDB-55755: Structure of the human inner kinetochore CCAN bound to a 3' CENP-A nucleosome
Method: EM (single particle) / Resolution: 9.5 Å

EMDB-55756: Structure of the human inner kinetochore CCAN bound to a 5' CENP-A nucleosome
Method: EM (single particle) / Resolution: 15.5 Å

55757

9taw

EMDB-55757, PDB-9taw:
Structure of the human inner kinetochore CCAN bound to DNA
Method: EM (single particle) / Resolution: 3.54 Å

55758

9tax

EMDB-55758, PDB-9tax:
Structure of the human inner kinetochore CCAN bound to a mono-CENP-A nucleosome
Method: EM (single particle) / Resolution: 4.5 Å

55759

9tay

EMDB-55759, PDB-9tay:
Structure of the human inner kinetochore CCAN bound to a di-CENP-A nucleosome
Method: EM (single particle) / Resolution: 15.5 Å

EMDB-56612: Structure of the human inner kinetochore CCAN bound to a di-CENP-A nucleosome, consensus map
Method: EM (single particle) / Resolution: 10.9 Å

56683

28op

EMDB-56683, PDB-28op:
Structure of the human inner kinetochore CCAN and CENP-C bound to DNA
Method: EM (single particle) / Resolution: 2.7 Å

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • trichoplusia ni (cabbage looper)
KeywordsCELL CYCLE / Centromeres / Kinetochores

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