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Basic information
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Title | Human 20S proteasome assembly intermediate structure 4 | |||||||||||||||
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![]() | Complex / HYDROLASE | |||||||||||||||
Function / homology | ![]() cerebellar granule cell precursor proliferation / purine ribonucleoside triphosphate binding / regulation of endopeptidase activity / protein folding chaperone complex / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / proteasome core complex assembly / immune system process ...cerebellar granule cell precursor proliferation / purine ribonucleoside triphosphate binding / regulation of endopeptidase activity / protein folding chaperone complex / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / proteasome core complex assembly / immune system process / myofibril / proteasome binding / mitotic spindle assembly checkpoint signaling / NF-kappaB binding / proteasome assembly / chaperone-mediated protein complex assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / negative regulation of inflammatory response to antigenic stimulus / : / sarcomere / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / proteolysis involved in protein catabolic process / Autodegradation of Cdh1 by Cdh1:APC/C / 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 / Assembly of the pre-replicative complex / 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 / lipopolysaccharide binding / SCF(Skp2)-mediated degradation of p27/p21 / 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 / Negative regulation of NOTCH4 signaling / Defective CFTR causes cystic fibrosis / 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 / P-body / 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 / response to virus / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / ABC-family proteins mediated transport / response to organic cyclic compound / CLEC7A (Dectin-1) signaling / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / nuclear matrix / 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 / regulation of inflammatory response / Downstream TCR signaling / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / positive regulation of NF-kappaB transcription factor activity / peptidase activity / ER-Phagosome pathway / endopeptidase activity / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / response to oxidative stress / ficolin-1-rich granule lumen / postsynapse / molecular adaptor activity / nuclear body / ribosome / Ub-specific processing proteases / nuclear speck / intracellular membrane-bounded organelle Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.95 Å | |||||||||||||||
![]() | Schulman BA / Hanna JW / Harper JW / Adolf F / Du J / Rawson SD / Walsh Jr RM / Goodall EA | |||||||||||||||
Funding support | ![]() ![]()
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![]() | Journal: bioRxiv / Year: 2024 Title: Visualizing chaperone-mediated multistep assembly of the human 20S proteasome. Authors: Frank Adolf / Jiale Du / Ellen A Goodall / Richard M Walsh / Shaun Rawson / Susanne von Gronau / J Wade Harper / John Hanna / Brenda A Schulman / ![]() ![]() Abstract: Dedicated assembly factors orchestrate stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here, we report cryo- ...Dedicated assembly factors orchestrate stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here, we report cryo-EM reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. Comparison of these chaperone-bound intermediates and a matching mature CP reveals molecular mechanisms determining the order of successive subunit additions, and how proteasome subcomplexes and assembly factors structurally adapt upon progressive subunit incorporation to stabilize intermediates, facilitate the formation of subsequent intermediates, and ultimately rearrange to coordinate proteolytic activation with gated access to active sites. The structural findings reported here explain many previous biochemical and genetic observations. This work establishes a methodologic approach for structural analysis of multiprotein complex assembly intermediates, illuminates specific functions of assembly factors, and reveals conceptual principles underlying human proteasome biogenesis. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 53 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 35.6 KB 35.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.9 KB | Display | ![]() |
Images | ![]() | 68.1 KB | ||
Masks | ![]() | 103 MB | ![]() | |
Filedesc metadata | ![]() | 8.8 KB | ||
Others | ![]() ![]() ![]() | 88.1 MB 95.5 MB 95.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8qz9MC ![]() 8qyjC ![]() 8qylC ![]() 8qymC ![]() 8qynC ![]() 8qyoC ![]() 8qysC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.8512 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Additional map: #1
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-Half map: #2
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-Half map: #1
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Sample components
+Entire : Human 20S proteasome assembly intermediate map 4
+Supramolecule #1: Human 20S proteasome assembly intermediate map 4
+Macromolecule #1: Proteasome subunit alpha type-2
+Macromolecule #2: Proteasome subunit alpha type-4
+Macromolecule #3: Proteasome subunit alpha type-7
+Macromolecule #4: Proteasome subunit alpha type-5
+Macromolecule #5: Proteasome subunit alpha type-1
+Macromolecule #6: Proteasome subunit alpha type-3
+Macromolecule #7: Proteasome subunit alpha type-6
+Macromolecule #8: Proteasome maturation protein
+Macromolecule #9: Proteasome assembly chaperone 1
+Macromolecule #10: Proteasome assembly chaperone 2
+Macromolecule #11: Proteasome subunit beta type-7
+Macromolecule #12: Proteasome subunit beta type-3
+Macromolecule #13: Proteasome subunit beta type-2
+Macromolecule #14: Proteasome subunit beta type-5
+Macromolecule #15: Proteasome subunit beta type-1
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 66.9 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |