6SEF

Class2C : CENP-A nucleosome in complex with CENP-C central region

Summary for 6SEF

• Entry DOI: 10.2210/pdb6sef/pdb
• EMDB information: 10154
• Descriptor: Histone H3-like centromeric protein A, Histone H4, Histone H2A type 2-A, ... (7 entities in total)
• Functional Keywords: cenp-a, nucleosome, centromere, centromeric chromatin, nuclear protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 11
• Total formula weight: 214678.43

Authors

Ali-Ahmad, A.,Bilokapic, S.,Schafer, I.B.,Halic, M.,Sekulic, N. (deposition date: 2019-07-29, release date: 2019-08-14, Last modification date: 2024-05-22)

Primary citation

Ali-Ahmad, A.,Bilokapic, S.,Schafer, I.B.,Halic, M.,Sekulic, N.
CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail.
Embo Rep., 20:e48913-e48913, 2019

PubMed Abstract: Centromeres are defined epigenetically by nucleosomes containing the histone H3 variant CENP-A, upon which the constitutive centromere-associated network of proteins (CCAN) is built. CENP-C is considered to be a central organizer of the CCAN. We provide new molecular insights into the structure of human CENP-A nucleosomes, in isolation and in complex with the CENP-C central region (CENP-C ), the main CENP-A binding module of human CENP-C. We establish that the short αN helix of CENP-A promotes DNA flexibility at the nucleosome ends, independently of the sequence it wraps. Furthermore, we show that, in vitro, two regions of human CENP-C (CENP-C and CENP-C ) both bind exclusively to the CENP-A nucleosome. We find CENP-C to bind with high affinity due to an extended hydrophobic area made up of CENP-A and CENP-A . Importantly, we identify two key conformational changes within the CENP-A nucleosome upon CENP-C binding. First, the loose DNA wrapping of CENP-A nucleosomes is further exacerbated, through destabilization of the H2A C-terminal tail. Second, CENP-C rigidifies the N-terminal tail of H4 in the conformation favoring H4 monomethylation, essential for a functional centromere.

PubMed: 31475439
DOI: 10.15252/embr.201948913

Experimental method

ELECTRON MICROSCOPY (3.7 Å)