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TitleStructure of the human inner kinetochore CCAN complex and its significance for human centromere organization.
Journal, issue, pagesMol Cell, Vol. 82, Issue 11, Page 2113-22131.e8, Year 2022
Publish dateMay 6, 2022
AuthorsMarion E Pesenti / Tobias Raisch / Duccio Conti / Kai Walstein / Ingrid Hoffmann / Dorothee Vogt / Daniel Prumbaum / Ingrid R Vetter / Stefan Raunser / Andrea Musacchio /
PubMed AbstractCentromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. A 16-subunit complex, the constitutive centromere associated ...Centromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. A 16-subunit complex, the constitutive centromere associated network (CCAN), connects between the specialized centromeric chromatin, marked by the histone H3 variant CENP-A, and the spindle-binding moiety of the kinetochore. Here, we report a cryo-electron microscopy structure of human CCAN. We highlight unique features such as the pseudo GTPase CENP-M and report how a crucial CENP-C motif binds the CENP-LN complex. The CCAN structure has implications for the mechanism of specific recognition of the CENP-A nucleosome. A model consistent with our structure depicts the CENP-C-bound nucleosome as connected to the CCAN through extended, flexible regions of CENP-C. An alternative model identifies both CENP-C and CENP-N as specificity determinants but requires CENP-N to bind CENP-A in a mode distinct from the classical nucleosome octamer.
External linksMol Cell / PubMed:35525244 / PubMed Central
MethodsEM (single particle)
Resolution4.6 - 10.0 Å
Structure data

14098

7qoo

EMDB-14098, PDB-7qoo:
Structure of the human inner kinetochore CCAN complex
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-14099: STRUCTURE OF THE HUMAN INNER KINETOCHORE CCAN COMPLEX AT 10A RESOLUTION
Method: EM (single particle) / Resolution: 10.0 Å

Source
  • homo sapiens (human)
KeywordsCELL CYCLE / INNER KINETOCHORE / CCAN / COMPLEX / DNA BINDING PROTEIN

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