- EMDB-34431: Cryo-EM structure of BAP1-ASXL1 bound to chromatosome -
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Entry
Database: EMDB / ID: EMD-34431
Title
Cryo-EM structure of BAP1-ASXL1 bound to chromatosome
Map data
Sample
Complex: Cryo-EM structure of BAP1-ASXL1 bound to chromatosome
Protein or peptide: Histone H3.1Histone H3
Protein or peptide: Histone H4
Protein or peptide: Histone H2A type 1-D
Protein or peptide: Histone H2B type 2-E
DNA: DNA (187-MER)
DNA: DNA (187-MER)
Protein or peptide: Histone H1.4
Protein or peptide: Ubiquitin carboxyl-terminal hydrolase BAP1
Protein or peptide: Ubiquitin
Protein or peptide: Polycomb group protein ASXL1Polycomb-group proteins
Function / homology
Function and homology information
thrombocyte differentiation / nucleate erythrocyte differentiation / negative regulation of peroxisome proliferator activated receptor signaling pathway / PR-DUB complex / leukocyte proliferation / platelet morphogenesis / histone H2A deubiquitinase activity / positive regulation of retinoic acid receptor signaling pathway / macrophage homeostasis / lung saccule development ...thrombocyte differentiation / nucleate erythrocyte differentiation / negative regulation of peroxisome proliferator activated receptor signaling pathway / PR-DUB complex / leukocyte proliferation / platelet morphogenesis / histone H2A deubiquitinase activity / positive regulation of retinoic acid receptor signaling pathway / macrophage homeostasis / lung saccule development / podocyte development / neutrophil differentiation / regulation of kidney size / myeloid cell apoptotic process / hematopoietic stem cell homeostasis / monoubiquitinated protein deubiquitination / common myeloid progenitor cell proliferation / protein K48-linked deubiquitination / negative regulation of DNA recombination / tissue homeostasis / nuclear retinoic acid receptor binding / Apoptosis induced DNA fragmentation / hypothalamus gonadotrophin-releasing hormone neuron development / peroxisome proliferator activated receptor binding / chromosome condensation / bone marrow development / female meiosis I / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule / positive regulation of protein targeting to mitochondrion / fat pad development / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / female gonad development / negative regulation of fat cell differentiation / seminiferous tubule development / protein deubiquitination / male meiosis I / erythrocyte maturation / regulation of cytokine production involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / hemopoiesis / homeostasis of number of cells / : / negative regulation of megakaryocyte differentiation / nucleosomal DNA binding / protein localization to CENP-A containing chromatin / heterochromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / epigenetic regulation of gene expression / energy homeostasis / regulation of neuron apoptotic process / Packaging Of Telomere Ends / heart morphogenesis / regulation of proteasomal protein catabolic process / response to retinoic acid / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Maturation of protein E / Maturation of protein E / Deposition of new CENPA-containing nucleosomes at the centromere / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Inhibition of DNA recombination at telomere / Meiotic synapsis / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / telomere organization / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Pexophagy / Regulation of innate immune responses to cytosolic DNA / VLDLR internalisation and degradation / InlA-mediated entry of Listeria monocytogenes into host cells / Downregulation of ERBB2:ERBB3 signaling / RNA Polymerase I Promoter Opening / NF-kB is activated and signals survival Similarity search - Function
National Natural Science Foundation of China (NSFC)
31991162
China
National Natural Science Foundation of China (NSFC)
918532204
China
National Natural Science Foundation of China (NSFC)
92153302
China
Citation
Journal: Nature / Year: 2023 Title: Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase. Authors: Weiran Ge / Cong Yu / Jingjing Li / Zhenyu Yu / Xiaorong Li / Yan Zhang / Chao-Pei Liu / Yingfeng Li / Changlin Tian / Xinzheng Zhang / Guohong Li / Bing Zhu / Rui-Ming Xu / Abstract: Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification. The Polycomb repressive ...Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification. The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119ub1) on the nucleosome, counteracting the ubiquitin E3 ligase activity of Polycomb repressive complex 1 (PRC1) to facilitate the correct silencing of genes by Polycomb proteins and safeguard active genes from inadvertent silencing by PRC1 (refs. ). The intricate biological function of PR-DUB requires accurate targeting of H2AK119ub1, but PR-DUB can deubiquitinate monoubiquitinated free histones and peptide substrates indiscriminately; the basis for its exquisite nucleosome-dependent substrate specificity therefore remains unclear. Here we report the cryo-electron microscopy structure of human PR-DUB, composed of BAP1 and ASXL1, in complex with the chromatosome. We find that ASXL1 directs the binding of the positively charged C-terminal extension of BAP1 to nucleosomal DNA and histones H3-H4 near the dyad, an addition to its role in forming the ubiquitin-binding cleft. Furthermore, a conserved loop segment of the catalytic domain of BAP1 is situated near the H2A-H2B acidic patch. This distinct nucleosome-binding mode displaces the C-terminal tail of H2A from the nucleosome surface, and endows PR-DUB with the specificity for H2AK119ub1.
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