CENP-A containing chromatin assembly / protein localization to chromosome, centromeric region / kinetochore assembly / condensed chromosome, centromeric region / establishment of mitotic spindle orientation / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / mitotic cytokinesis / chromosome, centromeric region / Replacement of protamines by nucleosomes in the male pronucleus ...CENP-A containing chromatin assembly / protein localization to chromosome, centromeric region / kinetochore assembly / condensed chromosome, centromeric region / establishment of mitotic spindle orientation / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / mitotic cytokinesis / chromosome, centromeric region / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / pericentric heterochromatin / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / arachidonate metabolic process / lipid oxidation / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / nucleosomal DNA binding / Resolution of Sister Chromatid Cohesion / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Defective pyroptosis / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / RHO GTPases Activate Formins / Transcriptional regulation by small RNAs / Transcriptional regulation of granulopoiesis / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / structural constituent of chromatin / Separation of Sister Chromatids / UCH proteinases / nucleosome / antimicrobial humoral immune response mediated by antimicrobial peptide / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / E3 ubiquitin ligases ubiquitinate target proteins / Senescence-Associated Secretory Phenotype (SASP) / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / antibacterial humoral response / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation / chromatin binding / DNA binding / extracellular space / extracellular exosome / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol Similarity search - Function
Histone H3-like centromeric protein A / Arachidonate 15-lipoxygenase / Histone H2B type 1-C/E/F/G/I / Histone H2A type 2-A Similarity search - Component
Biological species
Homo sapiens (human) / synthetic construct (others)
Method
single particle reconstruction / cryo EM / Resolution: 4.2 Å
Journal: EMBO Rep / Year: 2019 Title: CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. Authors: Ahmad Ali-Ahmad / Silvija Bilokapić / Ingmar B Schäfer / Mario Halić / Nikolina Sekulić / 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 ...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.
History
Deposition
Jul 30, 2019
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Header (metadata) release
Aug 14, 2019
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Map release
Aug 14, 2019
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Update
Oct 16, 2019
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Current status
Oct 16, 2019
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
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