› 7w3b

Electron Microscopy
3.6Å resolution

Structure of USP14-bound human 26S proteasome in substrate-engaged state ED5_USP14

Released:
DOI: 10.2210/pdb7w3b/pdb
PDB entry 7w3b coloured by chain, front view.
PDB entry 7w3b coloured by chain, side view.
PDB entry 7w3b coloured by chain, top view.
Source organisms:
Primary publication:
USP14-regulated allostery of the human proteasome by time-resolved cryo-EM.
Zhang S, Zou S, Yin D, Zhao L, Finley D, Wu Z, Mao Y
Nature 605 567-574 (2022)
PMID: 35477760
Related structures: EMD-32276

Function and Biology Details

Reactions catalysed: 
Cleavage of peptide bonds with very broad specificity.
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero 49-mer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-100672 (preferred)
Entry contents:
35 distinct polypeptide molecules
Macromolecules (35 distinct):
26S proteasome regulatory subunit 7 Chain: A
Molecule details ›
Chain: A
Length: 433 amino acids
Theoretical weight: 48.7 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P35998 (Residues: 1-433; Coverage: 100%)
Gene names: MSS1, PSMC2
Sequence domains:
26S proteasome regulatory subunit 4 Chain: B
Molecule details ›
Chain: B
Length: 440 amino acids
Theoretical weight: 49.26 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P62191 (Residues: 1-440; Coverage: 100%)
Gene name: PSMC1
Sequence domains:
26S proteasome regulatory subunit 8 Chain: C
Molecule details ›
Chain: C
Length: 398 amino acids
Theoretical weight: 44.85 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P62195 (Residues: 9-406; Coverage: 98%)
Gene names: PSMC5, SUG1
Sequence domains:
26S proteasome regulatory subunit 6B Chain: D
Molecule details ›
Chain: D
Length: 418 amino acids
Theoretical weight: 47.43 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P43686 (Residues: 1-418; Coverage: 100%)
Gene names: MIP224, PSMC4, TBP7
Sequence domains:
AAA+ ATPase domain-containing protein Chain: E
Molecule details ›
Chain: E
Length: 403 amino acids
Theoretical weight: 45.87 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: A0A087X2I1 (Residues: 1-403; Coverage: 100%)
Gene name: PSMC6
Sequence domains:
26S proteasome regulatory subunit 6A Chain: F
Molecule details ›
Chain: F
Length: 439 amino acids
Theoretical weight: 49.27 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P17980 (Residues: 1-439; Coverage: 100%)
Gene names: PSMC3, TBP1
Sequence domains:
Proteasome subunit alpha type-6 Chains: G, g
Molecule details ›
Chains: G, g
Length: 246 amino acids
Theoretical weight: 27.43 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P60900 (Residues: 1-246; Coverage: 100%)
Gene names: PROS27, PSMA6
Sequence domains:
Proteasome subunit alpha type-2 Chains: H, h
Molecule details ›
Chains: H, h
Length: 234 amino acids
Theoretical weight: 25.93 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P25787 (Residues: 1-234; Coverage: 100%)
Gene names: HC3, PSC3, PSMA2
Sequence domains:
Proteasome subunit alpha type-4 Chains: I, i
Molecule details ›
Chains: I, i
Length: 261 amino acids
Theoretical weight: 29.53 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P25789 (Residues: 1-261; Coverage: 100%)
Gene names: HC9, PSC9, PSMA4
Sequence domains:
Proteasome subunit alpha type-7 Chains: J, j
Molecule details ›
Chains: J, j
Length: 248 amino acids
Theoretical weight: 27.93 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: O14818 (Residues: 1-248; Coverage: 100%)
Gene names: HSPC, PSMA7
Sequence domains:
Proteasome subunit alpha type-5 Chains: K, k
Molecule details ›
Chains: K, k
Length: 241 amino acids
Theoretical weight: 26.44 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P28066 (Residues: 1-241; Coverage: 100%)
Gene name: PSMA5
Sequence domains:
Proteasome subunit alpha type-1 Chains: L, l
Molecule details ›
Chains: L, l
Length: 269 amino acids
Theoretical weight: 30.28 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P25786 (Residues: 2-263; Coverage: 100%)
Gene names: HC2, NU, PROS30, PSC2, PSMA1
Sequence domains:
Proteasome subunit alpha type-3 Chains: M, m
Molecule details ›
Chains: M, m
Length: 255 amino acids
Theoretical weight: 28.47 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P25788 (Residues: 1-255; Coverage: 100%)
Gene names: HC8, PSC8, PSMA3
Sequence domains:
Proteasome subunit beta type-6 Chains: N, n
Molecule details ›
Chains: N, n
Length: 239 amino acids
Theoretical weight: 25.38 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P28072 (Residues: 1-239; Coverage: 100%)
Gene names: LMPY, PSMB6, Y
Sequence domains: Proteasome subunit
Proteasome subunit beta type-7 Chains: O, o
Molecule details ›
Chains: O, o
Length: 277 amino acids
Theoretical weight: 30 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q99436 (Residues: 1-277; Coverage: 100%)
Gene names: PSMB7, Z
Sequence domains:
Proteasome subunit beta type-3 Chains: P, p
Molecule details ›
Chains: P, p
Length: 205 amino acids
Theoretical weight: 22.97 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P49720 (Residues: 1-205; Coverage: 100%)
Gene name: PSMB3
Sequence domains: Proteasome subunit
Proteasome subunit beta type-2 Chains: Q, q
Molecule details ›
Chains: Q, q
Length: 201 amino acids
Theoretical weight: 22.86 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P49721 (Residues: 1-201; Coverage: 100%)
Gene name: PSMB2
Sequence domains: Proteasome subunit
Proteasome subunit beta type-5 Chains: R, r
Molecule details ›
Chains: R, r
Length: 263 amino acids
Theoretical weight: 28.51 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P28074 (Residues: 1-263; Coverage: 100%)
Gene names: LMPX, MB1, PSMB5, X
Sequence domains: Proteasome subunit
Proteasome subunit beta type-1 Chains: S, s
Molecule details ›
Chains: S, s
Length: 241 amino acids
Theoretical weight: 26.52 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P20618 (Residues: 1-241; Coverage: 100%)
Gene names: PSC5, PSMB1
Sequence domains: Proteasome subunit
Proteasome subunit beta type-4 Chains: T, t
Molecule details ›
Chains: T, t
Length: 264 amino acids
Theoretical weight: 29.23 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P28070 (Residues: 1-264; Coverage: 100%)
Gene names: PROS26, PSMB4
Sequence domains: Proteasome subunit
26S proteasome non-ATPase regulatory subunit 1 Chain: U
Molecule details ›
Chain: U
Length: 953 amino acids
Theoretical weight: 105.96 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q99460 (Residues: 1-953; Coverage: 100%)
Gene name: PSMD1
Sequence domains:
26S proteasome non-ATPase regulatory subunit 3 Chain: V
Molecule details ›
Chain: V
Length: 534 amino acids
Theoretical weight: 61.07 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: O43242 (Residues: 1-534; Coverage: 100%)
Gene name: PSMD3
Sequence domains:
26S proteasome non-ATPase regulatory subunit 12 Chain: W
Molecule details ›
Chain: W
Length: 456 amino acids
Theoretical weight: 52.98 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: O00232 (Residues: 1-456; Coverage: 100%)
Gene name: PSMD12
Sequence domains:
26S proteasome non-ATPase regulatory subunit 11 Chain: X
Molecule details ›
Chain: X
Length: 422 amino acids
Theoretical weight: 47.53 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: O00231 (Residues: 1-422; Coverage: 100%)
Gene name: PSMD11
Sequence domains:
26S proteasome non-ATPase regulatory subunit 6 Chain: Y
Molecule details ›
Chain: Y
Length: 389 amino acids
Theoretical weight: 45.59 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q15008 (Residues: 1-389; Coverage: 100%)
Gene names: KIAA0107, PFAAP4, PSMD6
Sequence domains:
26S proteasome non-ATPase regulatory subunit 7 Chain: Z
Molecule details ›
Chain: Z
Length: 324 amino acids
Theoretical weight: 37.09 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P51665 (Residues: 1-324; Coverage: 100%)
Gene names: MOV34L, PSMD7
Sequence domains:
26S proteasome non-ATPase regulatory subunit 13 Chain: a
Molecule details ›
Chain: a
Length: 376 amino acids
Theoretical weight: 43 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q9UNM6 (Residues: 1-376; Coverage: 100%)
Gene name: PSMD13
Sequence domains: PCI domain
26S proteasome non-ATPase regulatory subunit 4 Chain: b
Molecule details ›
Chain: b
Length: 377 amino acids
Theoretical weight: 40.78 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P55036 (Residues: 1-377; Coverage: 100%)
Gene names: MCB1, PSMD4
Sequence domains:
26S proteasome non-ATPase regulatory subunit 14 Chain: c
Molecule details ›
Chain: c
Length: 310 amino acids
Theoretical weight: 34.62 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: O00487 (Residues: 1-310; Coverage: 100%)
Gene names: POH1, PSMD14
Sequence domains: JAB1/Mov34/MPN/PAD-1 ubiquitin protease
26S proteasome non-ATPase regulatory subunit 8 Chain: d
Molecule details ›
Chain: d
Length: 350 amino acids
Theoretical weight: 39.67 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P48556 (Residues: 1-350; Coverage: 100%)
Gene name: PSMD8
Sequence domains: CSN8/PSMD8/EIF3K family
26S proteasome non-ATPase regulatory subunit 2 Chain: f
Molecule details ›
Chain: f
Length: 908 amino acids
Theoretical weight: 100.31 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: Q13200 (Residues: 1-908; Coverage: 100%)
Gene names: PSMD2, TRAP2
Sequence domains:
Substrate Chain: v
Molecule details ›
Chain: v
Length: 28 amino acids
Theoretical weight: 2.4 KDa
Source organism: Saccharomyces cerevisiae
Expression system: Escherichia coli BL21(DE3)
Ubiquitin carboxyl-terminal hydrolase 14 Chain: x
Molecule details ›
Chain: x
Length: 494 amino acids
Theoretical weight: 56.13 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P54578 (Residues: 1-494; Coverage: 100%)
Gene names: TGT, USP14
Sequence domains: Ubiquitin carboxyl-terminal hydrolase
Ubiquitin Chain: y
Molecule details ›
Chain: y
Length: 76 amino acids
Theoretical weight: 8.58 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P0CG47 (Residues: 153-228; Coverage: 33%)
Gene name: UBB
Sequence domains: Ubiquitin family
26S proteasome complex subunit SEM1 Chain: e
Molecule details ›
Chain: e
Length: 70 amino acids
Theoretical weight: 8.28 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: P60896 (Residues: 1-70; Coverage: 100%)
Gene names: C7orf76, DSS1, SEM1, SHFDG1, SHFM1
Sequence domains: DSS1/SEM1 family

Ligands and Environments

3 bound ligands:
Ligand ATP 3 x ATP
Ligand ADP 1 x ADP
Ligand ZN 1 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
Resolution: 3.6Å
Relevant EMDB volumes: EMD-32276
Expression systems:
  • Homo sapiens
  • Escherichia coli BL21(DE3)

Quick links

Citations

8 review citations

AlphaFold, allosteric, and orthosteric drug discovery: Ways forward.
Nussinov et al. (2023)
7 more