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-Structure paper
タイトル | CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. |
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ジャーナル・号・ページ | EMBO Rep, Vol. 20, Issue 10, Page e48913, Year 2019 |
掲載日 | 2019年10月4日 |
著者 | Ahmad Ali-Ahmad / Silvija Bilokapić / Ingmar B Schäfer / Mario Halić / Nikolina Sekulić / |
PubMed 要旨 | 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 ...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. |
リンク | EMBO Rep / PubMed:31475439 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 4.4 Å |
構造データ | EMDB-10151: CENP-A nucleosome EMDB-10152: CENP-A nucleosome in complex with CENP-C central region EMDB-10153, PDB-6see: EMDB-10154, PDB-6sef: EMDB-10155, PDB-6seg: EMDB-10156: EMDB-10157: EMDB-10158: EMDB-10159: |
由来 |
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キーワード | NUCLEAR PROTEIN / CENP-A / nucleosome / centromere / centromeric chromatin / CCAN / CENP-C |