+Open data
-Basic information
Entry | Database: PDB / ID: 6kwx | |||||||||
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Title | cryo-EM structure of human PA200 | |||||||||
Components | Proteasome activator complex subunit 4 | |||||||||
Keywords | HYDROLASE / Proteasome activator | |||||||||
Function / homology | Function and homology information spermatoproteasome complex / sperm DNA condensation / peptidase activator activity / Regulation of ornithine decarboxylase (ODC) / Cross-presentation of soluble exogenous antigens (endosomes) / proteasomal ubiquitin-independent protein catabolic process / proteasome binding / lysine-acetylated histone binding / Regulation of activated PAK-2p34 by proteasome mediated degradation / APC/C:Cdc20 mediated degradation of Securin ...spermatoproteasome complex / sperm DNA condensation / peptidase activator activity / Regulation of ornithine decarboxylase (ODC) / Cross-presentation of soluble exogenous antigens (endosomes) / proteasomal ubiquitin-independent protein catabolic process / proteasome binding / lysine-acetylated histone binding / Regulation of activated PAK-2p34 by proteasome mediated degradation / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / Vpu mediated degradation of CD4 / Degradation of DVL / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Hh mutants are degraded by ERAD / Degradation of AXIN / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / G2/M Checkpoints / Vif-mediated degradation of APOBEC3G / Autodegradation of the E3 ubiquitin ligase COP1 / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Orc1 removal from chromatin / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / MAPK6/MAPK4 signaling / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Degradation of beta-catenin by the destruction complex / ABC-family proteins mediated transport / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / CLEC7A (Dectin-1) signaling / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / Regulation of PTEN stability and activity / Interleukin-1 signaling / Regulation of RAS by GAPs / Separation of Sister Chromatids / Regulation of RUNX2 expression and activity / The role of GTSE1 in G2/M progression after G2 checkpoint / UCH proteinases / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / ER-Phagosome pathway / Ub-specific processing proteases / nuclear speck / DNA repair / DNA damage response / nucleoplasm / nucleus / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.75 Å | |||||||||
Authors | Ouyang, S. / Hongxin, G. | |||||||||
Funding support | China, 1items
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Citation | Journal: PLoS Biol / Year: 2020 Title: Cryo-EM structures of the human PA200 and PA200-20S complex reveal regulation of proteasome gate opening and two PA200 apertures. Authors: Hongxin Guan / Youwang Wang / Ting Yu / Yini Huang / Mianhuan Li / Abdullah F U H Saeed / Vanja Perčulija / Daliang Li / Jia Xiao / Dongmei Wang / Ping Zhu / Songying Ouyang / Abstract: Proteasomes are highly abundant and conserved protease complexes that eliminate unwanted proteins in the cells. As a single-chain ATP-independent nuclear proteasome activator, proteasome activator ...Proteasomes are highly abundant and conserved protease complexes that eliminate unwanted proteins in the cells. As a single-chain ATP-independent nuclear proteasome activator, proteasome activator 200 (PA200) associates with 20S core particle to form proteasome complex that catalyzes polyubiquitin-independent degradation of acetylated histones, thus playing a pivotal role in DNA repair and spermatogenesis. Here, we present cryo-electron microscopy (cryo-EM) structures of the human PA200-20S complex and PA200 at 2.72 Å and 3.75 Å, respectively. PA200 exhibits a dome-like architecture that caps 20S and uses its C-terminal YYA (Tyr-Tyr-Ala) to induce the α-ring rearrangements and partial opening of the 20S gate. Our structural data also indicate that PA200 has two openings formed by numerous positively charged residues that respectively bind (5,6)-bisdiphosphoinositol tetrakisphosphate (5,6[PP]2-InsP4) and inositol hexakisphosphate (InsP6) and are likely to be the gates that lead unfolded proteins through PA200 and into the 20S. Besides, our structural analysis of PA200 found that the bromodomain (BRD)-like (BRDL) domain of PA200 shows considerable sequence variation in comparison to other human BRDs, as it contains only 82 residues because of a short ZA loop, and cannot be classified into any of the eight typical human BRD families. Taken together, the results obtained from this study provide important insights into human PA200-induced 20S gate opening for substrate degradation and the opportunities to explore the mechanism for its recognition of H4 histone in acetylation-mediated proteasomal degradation. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6kwx.cif.gz | 330.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6kwx.ent.gz | 257.3 KB | Display | PDB format |
PDBx/mmJSON format | 6kwx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6kwx_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6kwx_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6kwx_validation.xml.gz | 58.7 KB | Display | |
Data in CIF | 6kwx_validation.cif.gz | 86.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kw/6kwx ftp://data.pdbj.org/pub/pdb/validation_reports/kw/6kwx | HTTPS FTP |
-Related structure data
Related structure data | 0780MC 0781C 6kwyC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 215774.875 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSME4, KIAA0077 / Production host: Homo sapiens (human) / References: UniProt: Q14997 |
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#2: Chemical | ChemComp-K0W / [( |
#3: Chemical | ChemComp-IHP / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human PA200 / Type: CELL / Entity ID: #1 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3.75 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 103000 / Symmetry type: POINT |