7R5R

Structure of the human CCAN CENP-A alpha-satellite complex

Summary for 7R5R

• Entry DOI: 10.2210/pdb7r5r/pdb
• EMDB information: 14334
• Descriptor: Histone H3-like centromeric protein A, Histone H4, Histone H2A type 1-C, ... (7 entities in total)
• Functional Keywords: chromosome, kinetochore, cell division, centromere, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 339979.84

Authors

Yatskevich, S.,Muir, K.W.,Bellini, D.,Zhang, Z.,Yang, J.,Tischer, T.,Predin, M.,Dendooven, T.,McLaughlin, S.H.,Barford, D. (deposition date: 2022-02-11, release date: 2022-04-27, Last modification date: 2024-07-17)

Primary citation

Yatskevich, S.,Muir, K.W.,Bellini, D.,Zhang, Z.,Yang, J.,Tischer, T.,Predin, M.,Dendooven, T.,McLaughlin, S.H.,Barford, D.
Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome.
Science, 376:844-852, 2022

PubMed Abstract: 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.

PubMed: 35420891
DOI: 10.1126/science.abn3810

Experimental method

ELECTRON MICROSCOPY (2.44 Å)