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Structure paper

TitleStructure of the human inner kinetochore bound to a centromeric CENP-A nucleosome.
Journal, issue, pagesScience, Vol. 376, Issue 6595, Page 844-852, Year 2022
Publish dateMay 20, 2022
AuthorsStanislau Yatskevich / Kyle W Muir / Dom Bellini / Ziguo Zhang / Jing Yang / Thomas Tischer / Masa Predin / Tom Dendooven / Stephen H McLaughlin / David Barford /
PubMed AbstractKinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-electron ...Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-electron microscopy structures of the human inner kinetochore constitutive centromere associated network (CCAN) complex bound to CENP-A reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-A, and a linker DNA segment of the α-satellite repeat emerges from the fully wrapped end of the nucleosome to thread through the central CENP-LN channel that tightly grips the DNA. The CENP-TWSX histone-fold module further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the linker DNA by CCAN provides a robust mechanism by which kinetochores withstand both pushing and pulling forces exerted by the mitotic spindle.
External linksScience / PubMed:35420891 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.44 - 12.0 Å
Structure data

13437

7pii

EMDB-13437, PDB-7pii:
Structure of the human CCAN CENP-A alpha-satellite complex
Method: EM (single particle) / Resolution: 2.68 Å

13473

7pkn

EMDB-13473, PDB-7pkn:
Structure of the human CCAN deltaCT complex
Method: EM (single particle) / Resolution: 3.2 Å

14334

7r5r

EMDB-14334, PDB-7r5r:
Structure of the human CCAN CENP-A alpha-satellite complex
Method: EM (single particle) / Resolution: 2.44 Å

14336

7r5s

EMDB-14336, PDB-7r5s:
Structure of the human CCAN bound to alpha satellite DNA
Method: EM (single particle) / Resolution: 2.83 Å

14341

7r5v

EMDB-14341, PDB-7r5v:
Structure of the human CCAN CENP-A alpha-satellite complex
Method: EM (single particle) / Resolution: 4.55 Å

14351

7ywx

EMDB-14351, PDB-7ywx:
Structure of the human CCAN CENP-A alpha-satellite complex
Method: EM (single particle) / Resolution: 12.0 Å

14375

7yyh

EMDB-14375, PDB-7yyh:
Structure of the human CCANdeltaT CENP-A alpha-satellite complex
Method: EM (single particle) / Resolution: 8.9 Å

PDB-7pb4:
Cenp-HIK 3-protein complex
Method: X-RAY DIFFRACTION / Resolution: 2.49 Å

PDB-7pb8:
Crystal structure of the CENP-OPQUR complex
Method: X-RAY DIFFRACTION / Resolution: 3.68 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsCELL CYCLE / inner kinetochore / Kinetochore / chromosome segregation / centromere / Chromosome / cell division

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