EMD-13473
Structure of the human CCAN deltaCT complex
EMD-13473
Single-particle3.2 Å
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Map released: 27/04/2022
Last modified: 17/07/2024
Sample Organism:
Homo sapiens
Sample: Human inner kinetochore CCAN
Fitted models: 7pkn (Avg. Q-score: 0.319)
Deposition Authors: Muir KW
,
Yatskevich S
,
Bellini D
,
Barford D
Sample: Human inner kinetochore CCAN
Fitted models: 7pkn (Avg. Q-score: 0.319)
Deposition Authors: Muir KW
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Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome.
Yatskevich S
,
Muir KW
,
Bellini D
,
Zhang Z
,
Yang J
,
Tischer T
,
Predin M
,
Dendooven T
,
McLaughlin SH
,
Barford D
(2022) Science , 376 , 844 - 852
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(2022) Science , 376 , 844 - 852
Abstract:
Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-ANuc) 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-ANuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, 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.
Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-ANuc) 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-ANuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, 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.