- EMDB-34954: Cryo-EM structure of SSX1 bound to the H2AK119Ub nucleosome at a ... -
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Entry
Database: EMDB / ID: EMD-34954
Title
Cryo-EM structure of SSX1 bound to the H2AK119Ub nucleosome at a resolution of 3.05 angstrom
Map data
Sample
Complex: SSX1-H2AK119Ub nucleosome complex
Protein or peptide: Histone H3
Protein or peptide: Histone H4 (Fragment)
Protein or peptide: Histone H2A type 1-B/E
Protein or peptide: Histone H2B type 1-K
Protein or peptide: Protein SSX2
Protein or peptide: Polyubiquitin-B (Fragment)
DNA: DNA (137-MER)
DNA: DNA (136-MER)
Protein or peptide: Histone H4
Protein or peptide: Histone H2A type 1-B/E
Keywords
SSX1 / H2AK119Ub nucleosome / Synovial Sarcoma / ssBAF / reader protein / STRUCTURAL PROTEIN
Function / homology
Function and homology information
protein localization to CENP-A containing chromatin / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / heterochromatin organization / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine ...protein localization to CENP-A containing chromatin / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / heterochromatin organization / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / innate immune response in mucosa / PRC2 methylates histones and DNA / Defective pyroptosis / HDACs deacetylate histones / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / 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 / G2/M DNA damage checkpoint / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / modification-dependent protein catabolic process / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / protein tag activity / UCH proteinases / nucleosome / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / Processing of DNA double-strand break ends / antibacterial humoral response / Senescence-Associated Secretory Phenotype (SASP) / Oxidative Stress Induced Senescence / defense response to Gram-negative bacterium / Estrogen-dependent gene expression / killing of cells of another organism / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein ubiquitination / protein heterodimerization activity / Amyloid fiber formation / negative regulation of cell population proliferation / ubiquitin protein ligase binding / regulation of DNA-templated transcription / DNA binding / extracellular space / extracellular exosome / nucleoplasm / nucleus / cytoplasm / cytosol Similarity search - Function
National Natural Science Foundation of China (NSFC)
22137005, 92253302
China
Other government
2022TQ0170,2022M720075
China
Citation
Journal: Nat Struct Mol Biol / Year: 2024 Title: Synovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes. Authors: Zebin Tong / Huasong Ai / Ziyu Xu / Kezhang He / Guo-Chao Chu / Qiang Shi / Zhiheng Deng / Qiaomei Xue / Maoshen Sun / Yunxiang Du / Lujun Liang / Jia-Bin Li / Man Pan / Lei Liu / Abstract: The cancer-specific fusion oncoprotein SS18-SSX1 disturbs chromatin accessibility by hijacking the BAF complex from the promoters and enhancers to the Polycomb-repressed chromatin regions. This ...The cancer-specific fusion oncoprotein SS18-SSX1 disturbs chromatin accessibility by hijacking the BAF complex from the promoters and enhancers to the Polycomb-repressed chromatin regions. This process relies on the selective recognition of H2AK119Ub nucleosomes by synovial sarcoma X breakpoint 1 (SSX1). However, the mechanism underlying the selective recognition of H2AK119Ub nucleosomes by SSX1 in the absence of ubiquitin (Ub)-binding capacity remains unknown. Here we report the cryo-EM structure of SSX1 bound to H2AK119Ub nucleosomes at 3.1-Å resolution. Combined in vitro biochemical and cellular assays revealed that the Ub recognition by SSX1 is unique and depends on a cryptic basic groove formed by H3 and the Ub motif on the H2AK119 site. Moreover, this unorthodox binding mode of SSX1 induces DNA unwrapping at the entry/exit sites. Together, our results describe a unique mode of site-specific ubiquitinated nucleosome recognition that underlies the specific hijacking of the BAF complex to Polycomb regions by SS18-SSX1 in synovial sarcoma.
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