7r5r

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

Structural highlights

7r5r is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.44Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CENPA_HUMAN Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).[1] [2]

Publication Abstract from PubMed

Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A(Nuc)) 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(Nuc) reconstituted onto alpha-satellite DNA. CCAN forms edge-on contacts with CENP-A(Nuc), and a linker DNA segment of the alpha-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.

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 Science. 2022 May 20;376(6595):844-852. doi: 10.1126/science.abn3810. Epub 2022 , Apr 14. PMID:35420891[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Aug 25. PMID:20739937 doi:10.1038/nature09323
  2. ↑ Hu H, Liu Y, Wang M, Fang J, Huang H, Yang N, Li Y, Wang J, Yao X, Shi Y, Li G, Xu RM. Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP. Genes Dev. 2011 May 1;25(9):901-6. Epub 2011 Apr 8. PMID:21478274 doi:10.1101/gad.2045111
  3. ↑ Yatskevich S, Muir KW, Bellini D, Zhang Z, Yang J, Tischer T, Predin M, Dendooven T, McLaughlin SH, Barford D. Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome. Science. 2022 May 20;376(6595):844-852. PMID:35420891 doi:10.1126/science.abn3810

Contents


PDB ID 7r5r

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OCA

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