Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization.
CCAN
CENP-A
CENP-C
CENP-L
CENP-N
CENP-TW
centromere
hemisome
kinetochore
nucleosome
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
02 06 2022
02 06 2022
Historique:
received:
14
01
2022
revised:
01
04
2022
accepted:
22
04
2022
pubmed:
8
5
2022
medline:
9
6
2022
entrez:
7
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35525244
pii: S1097-2765(22)00390-2
doi: 10.1016/j.molcel.2022.04.027
pmc: PMC9235857
pii:
doi:
Substances chimiques
Centromere Protein A
0
Nucleosomes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2113-2131.e8Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors have no interest to declare.
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