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Open data
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Basic information
Entry | Database: PDB / ID: 7dr6 | ||||||
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Title | PA28alpha-beta in complex with immunoproteasome | ||||||
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![]() | HYDROLASE / proteasome / PA28 alpha / PA28 beta / immunoproteasome | ||||||
Function / homology | ![]() Cross-presentation of soluble exogenous antigens (endosomes) / Regulation of ornithine decarboxylase (ODC) / proteasome activator complex / spermatoproteasome complex / Activation of NF-kappaB in B cells / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 ...Cross-presentation of soluble exogenous antigens (endosomes) / Regulation of ornithine decarboxylase (ODC) / proteasome activator complex / spermatoproteasome complex / Activation of NF-kappaB in B cells / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of AXIN / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / CLEC7A (Dectin-1) signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / Assembly of the pre-replicative complex / Orc1 removal from chromatin / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX2 expression and activity / Regulation of RUNX3 expression and activity / Regulation of PTEN stability and activity / Interleukin-1 signaling / KEAP1-NFE2L2 pathway / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Degradation of beta-catenin by the destruction complex / Neddylation / antigen processing and presentation of exogenous antigen / Antigen processing: Ubiquitination & Proteasome degradation / UCH proteinases / ABC-family proteins mediated transport / Ub-specific processing proteases / Downstream TCR signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Separation of Sister Chromatids / AUF1 (hnRNP D0) binds and destabilizes mRNA / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / proteasome core complex / Regulation of ornithine decarboxylase (ODC) / Cross-presentation of soluble exogenous antigens (endosomes) / Neutrophil degranulation / Somitogenesis / immune system process / fat cell differentiation / regulation of G1/S transition of mitotic cell cycle / antigen processing and presentation / endopeptidase activator activity / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / regulation of proteasomal protein catabolic process / negative regulation of inflammatory response to antigenic stimulus / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / Autodegradation of Cdh1 by Cdh1:APC/C / proteolysis involved in protein catabolic process / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Degradation of DVL / 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 / lipopolysaccharide binding / Degradation of AXIN / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Defective CFTR causes cystic fibrosis / Hedgehog ligand biogenesis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / G2/M Checkpoints / Vif-mediated degradation of APOBEC3G / Autodegradation of the E3 ubiquitin ligase COP1 / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / Degradation of GLI2 by the proteasome Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||
![]() | Cong, Y. / Xu, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM of mammalian PA28αβ-iCP immunoproteasome reveals a distinct mechanism of proteasome activation by PA28αβ. Authors: Jinhuan Chen / Yifan Wang / Cong Xu / Kaijian Chen / Qiaoyu Zhao / Shutian Wang / Yue Yin / Chao Peng / Zhanyu Ding / Yao Cong / ![]() Abstract: The proteasome activator PA28αβ affects MHC class I antigen presentation by associating with immunoproteasome core particles (iCPs). However, due to the lack of a mammalian PA28αβ-iCP structure, ...The proteasome activator PA28αβ affects MHC class I antigen presentation by associating with immunoproteasome core particles (iCPs). However, due to the lack of a mammalian PA28αβ-iCP structure, how PA28αβ regulates proteasome remains elusive. Here we present the complete architectures of the mammalian PA28αβ-iCP immunoproteasome and free iCP at near atomic-resolution by cryo-EM, and determine the spatial arrangement between PA28αβ and iCP through XL-MS. Our structures reveal a slight leaning of PA28αβ towards the α3-α4 side of iCP, disturbing the allosteric network of the gatekeeper α2/3/4 subunits, resulting in a partial open iCP gate. We find that the binding and activation mechanism of iCP by PA28αβ is distinct from those of constitutive CP by the homoheptameric TbPA26 or PfPA28. Our study sheds lights on the mechanism of enzymatic activity stimulation of immunoproteasome and suggests that PA28αβ-iCP has experienced profound remodeling during evolution to achieve its current level of function in immune response. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.3 MB | Display | ![]() |
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PDB format | ![]() | 1.1 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 167.3 KB | Display | |
Data in CIF | ![]() | 259.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30824MC ![]() 7dr7C ![]() 7drwC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Proteasome subunit alpha type- ... , 7 types, 14 molecules LeMfNgOaPbQcRd
#1: Protein | Mass: 27432.459 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #2: Protein | Mass: 25927.535 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #3: Protein | Mass: 29525.842 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #4: Protein | Mass: 27911.912 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #5: Protein | Mass: 26435.977 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #6: Protein | Mass: 29625.654 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #7: Protein | Mass: 28441.197 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Proteasome activator complex subunit ... , 2 types, 7 molecules ADFBCEG
#8: Protein | Mass: 27398.600 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #9: Protein | Mass: 28768.141 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Proteasome subunit beta type- ... , 7 types, 14 molecules HSITJUKVWZX1Y2
#10: Protein | Mass: 23016.947 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P33672, proteasome endopeptidase complex #11: Protein | Mass: 22924.309 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q5E9K0, proteasome endopeptidase complex #12: Protein | Mass: 26278.059 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q2TBX6, proteasome endopeptidase complex #13: Protein | Mass: 29057.018 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q3T108, proteasome endopeptidase complex #14: Protein | Mass: 23427.428 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q3SZC2, proteasome endopeptidase complex #15: Protein | Mass: 29128.318 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q3T0T1, proteasome endopeptidase complex #16: Protein | Mass: 30304.332 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q3T112, proteasome endopeptidase complex |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: 20S proteasome purified from bovine spleen in complex of human PA28 Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 38 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.10.1_2155: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45030 / Symmetry type: POINT | ||||||||||||||||||||||||
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