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Basic information

Entry
Database: PDB / ID: 9rkz
TitleCryoEM structure of human 20S proteasome in complex with proteasome inhibitor CP-17
Components
  • (Proteasome subunit alpha type- ...) x 7
  • (Proteasome subunit beta type- ...) x 7
KeywordsHYDROLASE
Function / homology
Function and homology information


purine ribonucleoside triphosphate binding / Antigen processing: Ub, ATP-independent proteasomal degradation / sperm glycocalyx / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / proteasome core complex / perinuclear theca / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / myofibril ...purine ribonucleoside triphosphate binding / Antigen processing: Ub, ATP-independent proteasomal degradation / sperm glycocalyx / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / proteasome core complex / perinuclear theca / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / myofibril / proteasomal ubiquitin-independent protein catabolic process / sperm head-tail coupling apparatus / immune system process / proteasome endopeptidase complex / NF-kappaB binding / proteasome core complex, beta-subunit complex / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / proteasome assembly / : / ciliary tip / proteasome complex / sarcomere / Regulation of activated PAK-2p34 by proteasome mediated degradation / Autodegradation of Cdh1 by Cdh1:APC/C / centriole / APC/C:Cdc20 mediated degradation of Securin / sperm end piece / negative regulation of inflammatory response to antigenic stimulus / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / lipopolysaccharide binding / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / P-body / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of DVL / Degradation of AXIN / Degradation of CRY and PER proteins / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / G2/M Checkpoints / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / Regulation of RUNX3 expression and activity / Autodegradation of the E3 ubiquitin ligase COP1 / Defective CFTR causes cystic fibrosis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Hedgehog 'on' state / Vif-mediated degradation of APOBEC3G / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / MAPK6/MAPK4 signaling / Degradation of CDH1 / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / CDK-mediated phosphorylation and removal of Cdc6 / ABC-family protein mediated transport / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / response to virus / FCERI mediated NF-kB activation / nuclear matrix / Regulation of expression of SLITs and ROBOs / Regulation of PTEN stability and activity / Interleukin-1 signaling / Orc1 removal from chromatin / Regulation of RUNX2 expression and activity / Regulation of RAS by GAPs / The role of GTSE1 in G2/M progression after G2 checkpoint / Separation of Sister Chromatids / UCH proteinases / KEAP1-NFE2L2 pathway / peptidase activity / Downstream TCR signaling / Antigen processing: Ubiquitination & Proteasome degradation / sperm principal piece / RUNX1 regulates transcription of genes involved in differentiation of HSCs / ER-Phagosome pathway / Neddylation / regulation of inflammatory response / response to oxidative stress / sperm midpiece / secretory granule lumen / endopeptidase activity / ficolin-1-rich granule lumen / proteasome-mediated ubiquitin-dependent protein catabolic process / positive regulation of canonical NF-kappaB signal transduction / Ub-specific processing proteases / cilium / nuclear body
Similarity search - Function
Proteasome subunit alpha 1 / Proteasome beta subunit, C-terminal / Proteasome beta subunits C terminal / Proteasome subunit beta 4 / Proteasome subunit beta 2 / Proteasome beta 3 subunit / Proteasome subunit alpha5 / Proteasome subunit alpha6 / Proteasome beta-type subunits signature. / Peptidase T1A, proteasome beta-subunit ...Proteasome subunit alpha 1 / Proteasome beta subunit, C-terminal / Proteasome beta subunits C terminal / Proteasome subunit beta 4 / Proteasome subunit beta 2 / Proteasome beta 3 subunit / Proteasome subunit alpha5 / Proteasome subunit alpha6 / Proteasome beta-type subunits signature. / Peptidase T1A, proteasome beta-subunit / Proteasome beta-type subunit, conserved site / Proteasome subunit A N-terminal signature / Proteasome alpha-type subunits signature. / Proteasome alpha-subunit, N-terminal domain / Proteasome subunit A N-terminal signature Add an annotation / Proteasome B-type subunit / Proteasome beta-type subunit profile. / : / Proteasome alpha-type subunit / Proteasome alpha-type subunit profile. / Proteasome subunit / Proteasome, subunit alpha/beta / Nucleophile aminohydrolases, N-terminal
Similarity search - Domain/homology
: / Proteasome subunit alpha type-7 / Proteasome subunit beta type-1 / Proteasome subunit alpha type-1 / Proteasome subunit alpha type-2 / Proteasome subunit alpha type-3 / Proteasome subunit alpha type-4 / Proteasome subunit alpha type-5 / Proteasome subunit beta type-4 / Proteasome subunit beta type-6 ...: / Proteasome subunit alpha type-7 / Proteasome subunit beta type-1 / Proteasome subunit alpha type-1 / Proteasome subunit alpha type-2 / Proteasome subunit alpha type-3 / Proteasome subunit alpha type-4 / Proteasome subunit alpha type-5 / Proteasome subunit beta type-4 / Proteasome subunit beta type-6 / Proteasome subunit beta type-5 / Proteasome subunit beta type-3 / Proteasome subunit beta type-2 / Proteasome subunit alpha type-6 / Proteasome subunit beta type-7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.95 Å
AuthorsBenova, V. / Suelzen, H. / Boura, E. / Silhan, J. / Fajtova, P.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: CryoEM structure of human 20S proteasome in complex with proteasome inhibitor CP-17
Authors: Benova, V. / Suelzen, H. / Boura, E. / Silhan, J. / Fajtova, P.
History
DepositionJun 15, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 24, 2026Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jun 24, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Proteasome subunit alpha type-6
B: Proteasome subunit alpha type-2
C: Proteasome subunit alpha type-4
E: Proteasome subunit alpha type-5
F: Proteasome subunit alpha type-1
G: Proteasome subunit alpha type-3
J: Proteasome subunit beta type-3
K: Proteasome subunit beta type-2
M: Proteasome subunit beta type-1
N: Proteasome subunit beta type-4
D: Proteasome subunit alpha type-7
H: Proteasome subunit beta type-6
I: Proteasome subunit beta type-7
L: Proteasome subunit beta type-5
O: Proteasome subunit alpha type-6
P: Proteasome subunit alpha type-2
Q: Proteasome subunit alpha type-4
R: Proteasome subunit alpha type-5
S: Proteasome subunit alpha type-1
T: Proteasome subunit alpha type-3
V: Proteasome subunit beta type-3
W: Proteasome subunit beta type-2
X: Proteasome subunit beta type-1
Y: Proteasome subunit beta type-4
Z: Proteasome subunit alpha type-7
a: Proteasome subunit beta type-6
b: Proteasome subunit beta type-7
c: Proteasome subunit beta type-5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)718,16430
Polymers716,80428
Non-polymers1,3602
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

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Proteasome subunit alpha type- ... , 7 types, 14 molecules AOBPCQERFSGTDZ

#1: Protein Proteasome subunit alpha type-6 / 27 kDa prosomal protein / p27K / Macropain iota chain / Multicatalytic endopeptidase complex iota ...27 kDa prosomal protein / p27K / Macropain iota chain / Multicatalytic endopeptidase complex iota chain / Proteasome iota chain


Mass: 27432.459 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA6, PROS27
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P60900
#2: Protein Proteasome subunit alpha type-2 / Macropain subunit C3 / Multicatalytic endopeptidase complex subunit C3 / Proteasome component C3


Mass: 25927.535 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA2, HC3, PSC3
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P25787, proteasome endopeptidase complex
#3: Protein Proteasome subunit alpha type-4 / Macropain subunit C9 / Multicatalytic endopeptidase complex subunit C9 / Proteasome component C9 / ...Macropain subunit C9 / Multicatalytic endopeptidase complex subunit C9 / Proteasome component C9 / Proteasome subunit L


Mass: 29525.842 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA4, HC9, PSC9
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P25789, proteasome endopeptidase complex
#4: Protein Proteasome subunit alpha type-5 / Macropain zeta chain / Multicatalytic endopeptidase complex zeta chain / Proteasome zeta chain


Mass: 26435.977 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA5
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P28066, proteasome endopeptidase complex
#5: Protein Proteasome subunit alpha type-1 / 30 kDa prosomal protein / PROS-30 / Macropain subunit C2 / Multicatalytic endopeptidase complex ...30 kDa prosomal protein / PROS-30 / Macropain subunit C2 / Multicatalytic endopeptidase complex subunit C2 / Proteasome component C2 / Proteasome nu chain


Mass: 29595.627 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA1, HC2, NU, PROS30, PSC2
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P25786
#6: Protein Proteasome subunit alpha type-3 / Macropain subunit C8 / Multicatalytic endopeptidase complex subunit C8 / Proteasome component C8


Mass: 28469.252 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA3, HC8, PSC8
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P25788, proteasome endopeptidase complex
#11: Protein Proteasome subunit alpha type-7 / Proteasome subunit RC6-1 / Proteasome subunit XAPC7


Mass: 27929.891 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA7, HSPC
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: O14818

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Proteasome subunit beta type- ... , 7 types, 14 molecules JVKWMXNYHaIbLc

#7: Protein Proteasome subunit beta type-3 / Proteasome chain 13 / Proteasome component C10-II / Proteasome theta chain


Mass: 22841.701 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB3
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P49720, proteasome endopeptidase complex
#8: Protein Proteasome subunit beta type-2 / Macropain subunit C7-I / Multicatalytic endopeptidase complex subunit C7-I / Proteasome component C7-I


Mass: 22864.277 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB2
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P49721, proteasome endopeptidase complex
#9: Protein Proteasome subunit beta type-1 / Macropain subunit C5 / Multicatalytic endopeptidase complex subunit C5 / Proteasome component C5 / ...Macropain subunit C5 / Multicatalytic endopeptidase complex subunit C5 / Proteasome component C5 / Proteasome gamma chain


Mass: 23578.986 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB1, PSC5
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P20618, proteasome endopeptidase complex
#10: Protein Proteasome subunit beta type-4 / 26 kDa prosomal protein / PROS-26 / Macropain beta chain / Multicatalytic endopeptidase complex ...26 kDa prosomal protein / PROS-26 / Macropain beta chain / Multicatalytic endopeptidase complex beta chain / Proteasome beta chain / Proteasome chain 3 / HsN3


Mass: 24414.740 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB4, PROS26
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P28070, proteasome endopeptidase complex
#12: Protein Proteasome subunit beta type-6 / Macropain delta chain / Multicatalytic endopeptidase complex delta chain / Proteasome delta chain / ...Macropain delta chain / Multicatalytic endopeptidase complex delta chain / Proteasome delta chain / Proteasome subunit Y


Mass: 21921.836 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB6, LMPY, Y
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P28072, proteasome endopeptidase complex
#13: Protein Proteasome subunit beta type-7 / Macropain chain Z / Multicatalytic endopeptidase complex chain Z / Proteasome subunit Z


Mass: 25321.980 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB7, Z
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: Q99436, proteasome endopeptidase complex
#14: Protein Proteasome subunit beta type-5 / Macropain epsilon chain / Multicatalytic endopeptidase complex epsilon chain / Proteasome chain 6 / ...Macropain epsilon chain / Multicatalytic endopeptidase complex epsilon chain / Proteasome chain 6 / Proteasome epsilon chain / Proteasome subunit MB1 / Proteasome subunit X / Proteasome subunit beta-5 / beta-5


Mass: 22142.020 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB5, LMPX, MB1, X
Production host: Homo sapiens environmental sample (environmental samples)
References: UniProt: P28074, proteasome endopeptidase complex

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Non-polymers , 1 types, 2 molecules

#15: Chemical ChemComp-A1JHK / ~{N}-[(2~{S})-3-(1~{H}-indol-3-yl)-1-[[(2~{S})-3-(1~{H}-indol-3-yl)-1-[[(2~{S},3~{R},4~{S})-4-methyl-3,5-bis(oxidanyl)-1-phenyl-pentan-2-yl]amino]-1-oxidanylidene-propan-2-yl]amino]-1-oxidanylidene-propan-2-yl]hexanamide


Mass: 679.848 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C40H49N5O5 / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: CryoEM structure of human 20S proteasome in complex with proteasome inhibitor CP-17
Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1-#14 / Source: NATURAL
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
120 mM4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acidHEPES1
250 mMsodium chlorideNaCl1
30.25 mMTris(hydroxypropyl)phosphineTHP1
SpecimenConc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: 50 micromolar CP-17
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 0 %

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 254452 / Symmetry type: POINT

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