5VFR

Nucleotide-driven Triple-state Remodeling of the AAA-ATPase Channel in the Activated Human 26S Proteasome


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.0 of the entry. See complete history


Literature

Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome.

Zhu, Y.Wang, W.L.Yu, D.Ouyang, Q.Lu, Y.Mao, Y.

(2018) Nat Commun 9: 1360-1360

  • DOI: https://doi.org/10.1038/s41467-018-03785-w
  • Primary Citation of Related Structures:  
    5VFO, 5VFP, 5VFQ, 5VFR, 5VFS, 5VFT, 5VFU

  • PubMed Abstract: 

    The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase unfoldase in the regulatory particle (RP) control the gating of the substrate-translocation channel leading to the proteolytic chamber of the core particle (CP). Here we report three alternative states of the ATP-γ-S-bound human proteasome, in which the CP gates are asymmetrically open, visualized by cryo-EM at near-atomic resolutions. At least four nucleotides are bound to the AAA-ATPase ring in these open-gate states. Variation in nucleotide binding gives rise to an axial movement of the pore loops narrowing the substrate-translation channel, which exhibit remarkable structural transitions between the spiral-staircase and saddle-shaped-circle topologies. Gate opening in the CP is thus regulated by nucleotide-driven conformational changes of the AAA-ATPase unfoldase. These findings demonstrate an elegant mechanism of allosteric coordination among sub-machines within the human proteasome holoenzyme.


  • Organizational Affiliation

    Center for Quantitative Biology, Peking University, Beijing, 100871, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 1A [auth U]911Homo sapiensMutation(s): 0 
Gene Names: PSMD1
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GTEx:  ENSG00000173692 
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 3B [auth V]480Homo sapiensMutation(s): 0 
Gene Names: PSMD3
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GTEx:  ENSG00000108344 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 12C [auth W]456Homo sapiensMutation(s): 0 
Gene Names: PSMD12
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GTEx:  ENSG00000197170 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 11D [auth X]380Homo sapiensMutation(s): 0 
Gene Names: PSMD11
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GTEx:  ENSG00000108671 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 6E [auth Y]378Homo sapiensMutation(s): 0 
Gene Names: PSMD6KIAA0107PFAAP4
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GTEx:  ENSG00000163636 
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 7F [auth Z]286Homo sapiensMutation(s): 0 
Gene Names: PSMD7MOV34L
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GTEx:  ENSG00000103035 
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 13G [auth a]373Homo sapiensMutation(s): 0 
Gene Names: PSMD13
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GTEx:  ENSG00000185627 
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 4H [auth b]191Homo sapiensMutation(s): 0 
Gene Names: PSMD4MCB1
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GTEx:  ENSG00000159352 
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 14I [auth c]287Homo sapiensMutation(s): 0 
Gene Names: PSMD14POH1
EC: 3.4.19
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GTEx:  ENSG00000115233 
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 8J [auth d]257Homo sapiensMutation(s): 0 
Gene Names: PSMD8
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GTEx:  ENSG00000099341 
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
Sem1K [auth e]70Homo sapiensMutation(s): 0 
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GTEx:  ENSG00000127922 
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Entity ID: 12
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-6L [auth G],
Z [auth g]
240Homo sapiensMutation(s): 0 
Gene Names: PSMA6PROS27
EC: 3.4.25.1
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GTEx:  ENSG00000100902 
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Entity ID: 13
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-2AA [auth h],
M [auth H]
232Homo sapiensMutation(s): 0 
Gene Names: PSMA2HC3PSC3
EC: 3.4.25.1
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GTEx:  ENSG00000106588 
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Entity ID: 14
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-4BA [auth i],
N [auth I]
250Homo sapiensMutation(s): 0 
Gene Names: PSMA4HC9PSC9
EC: 3.4.25.1
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GTEx:  ENSG00000041357 
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Entity ID: 15
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-7CA [auth j],
O [auth J]
243Homo sapiensMutation(s): 0 
Gene Names: PSMA7HSPC
EC: 3.4.25.1
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GTEx:  ENSG00000101182 
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Entity ID: 16
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-5DA [auth k],
P [auth K]
234Homo sapiensMutation(s): 0 
Gene Names: PSMA5
EC: 3.4.25.1
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GTEx:  ENSG00000143106 
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Entity ID: 17
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-1EA [auth l],
Q [auth L]
238Homo sapiensMutation(s): 0 
Gene Names: PSMA1HC2NUPROS30PSC2
EC: 3.4.25.1
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GTEx:  ENSG00000129084 
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Entity ID: 18
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit alpha type-3FA [auth m],
R [auth M]
245Homo sapiensMutation(s): 0 
Gene Names: PSMA3HC8PSC8
EC: 3.4.25.1
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GTEx:  ENSG00000100567 
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Entity ID: 19
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-6GA [auth n],
S [auth N]
191Homo sapiensMutation(s): 0 
Gene Names: PSMB6LMPYY
EC: 3.4.25.1
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GTEx:  ENSG00000142507 
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Entity ID: 20
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-7HA [auth o],
T [auth O]
220Homo sapiensMutation(s): 0 
Gene Names: PSMB7Z
EC: 3.4.25.1
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GTEx:  ENSG00000136930 
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Entity ID: 21
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-3IA [auth p],
U [auth P]
204Homo sapiensMutation(s): 0 
Gene Names: PSMB3
EC: 3.4.25.1
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GTEx:  ENSG00000277791 
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Entity ID: 22
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-2JA [auth q],
V [auth Q]
199Homo sapiensMutation(s): 0 
Gene Names: PSMB2
EC: 3.4.25.1
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GTEx:  ENSG00000126067 
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Entity ID: 23
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-5KA [auth r],
W [auth R]
201Homo sapiensMutation(s): 0 
Gene Names: PSMB5LMPXMB1X
EC: 3.4.25.1
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GTEx:  ENSG00000100804 
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Entity ID: 24
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-1LA [auth s],
X [auth S]
213Homo sapiensMutation(s): 0 
Gene Names: PSMB1PSC5
EC: 3.4.25.1
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GTEx:  ENSG00000008018 
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Entity ID: 25
MoleculeChains Sequence LengthOrganismDetailsImage
Proteasome subunit beta type-4MA [auth t],
Y [auth T]
215Homo sapiensMutation(s): 0 
Gene Names: PSMB4PROS26
EC: 3.4.25.1
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GTEx:  ENSG00000159377 
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Entity ID: 26
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome regulatory subunit 7NA [auth A]399Homo sapiensMutation(s): 0 
Gene Names: PSMC2MSS1
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GTEx:  ENSG00000161057 
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Entity ID: 27
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome regulatory subunit 4OA [auth B]389Homo sapiensMutation(s): 0 
Gene Names: PSMC1
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GTEx:  ENSG00000100764 
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Entity ID: 28
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome regulatory subunit 8PA [auth C]392Homo sapiensMutation(s): 0 
Gene Names: PSMC5SUG1
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GTEx:  ENSG00000087191 
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Entity ID: 29
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome regulatory subunit 6BQA [auth D]380Homo sapiensMutation(s): 0 
Gene Names: PSMC4MIP224TBP7
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GTEx:  ENSG00000013275 
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Entity ID: 30
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome regulatory subunit 10BRA [auth E]375Homo sapiensMutation(s): 0 
Gene Names: PSMC6SUG2
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GTEx:  ENSG00000100519 
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Entity ID: 31
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome regulatory subunit 6ASA [auth F]396Homo sapiensMutation(s): 0 
Gene Names: PSMC3TBP1
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GTEx:  ENSG00000165916 
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Entity ID: 32
MoleculeChains Sequence LengthOrganismDetailsImage
26S proteasome non-ATPase regulatory subunit 2TA [auth f]908Homo sapiensMutation(s): 0 
Gene Names: PSMD2TRAP2
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GTEx:  ENSG00000175166 
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.11.1
RECONSTRUCTIONRELION

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-07-18
    Type: Initial release