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

Analyse Nucleotide-driven Triple-state Remodeling of the AAA-ATPase Channel in the… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB
5VFU
Type
protein
Length
12,887 residues
Chains
46
Method
electron microscopy
Collection
MolNFT v2 / PDB Bank
Contract
0xd58B01f6C18086e5202cdC5D7Ad3E41790360102
Owner
0xF4e1AA6f26B7DA48EeAD9B24a97927303eeA07b8
Resolution
5.8
Source
Homo sapiens
Molecule
26S proteasome non-ATPase regulatory subunit 1; 26S proteasome non-ATPase regulatory…
EC
3.4.19.-, 3.4.25.1
UniProt
Q99460, O43242, O00232, O00231, Q15008, P51665, Q9UNM6, P55036, O00487, P48556, P35998, P62191, P62195, P43686, P62333, P17980, P60900, P25787, P25789, O14818, P28066, P25786, P25788, P28072, Q99436, P49720, P49721, P28074, P20618, P28070, Q13200
Ligands
ZN
Pockets
20 · best druggability 0.87

Structure

electron microscopy · resolution 5.8 · 32 distinct chains · 46% helix, 12% strand (DSSP).

ChainMoleculeTypeResiduesSecondary structureUniProt
U26S proteasome non-ATPase regulatory subunit 1protein80661% helix, 0% strandQ99460
V26S proteasome non-ATPase regulatory subunit 3protein48064% helix, 1% strandO43242
W26S proteasome non-ATPase regulatory subunit 12protein45668% helix, 2% strandO00232
X26S proteasome non-ATPase regulatory subunit 11protein24166% helix, 2% strandO00231
Y26S proteasome non-ATPase regulatory subunit 6protein37865% helix, 2% strandQ15008
Z26S proteasome non-ATPase regulatory subunit 7protein28646% helix, 17% strandP51665
a26S proteasome non-ATPase regulatory subunit 13protein37365% helix, 2% strandQ9UNM6
b26S proteasome non-ATPase regulatory subunit 4protein19136% helix, 15% strandP55036
c26S proteasome non-ATPase regulatory subunit 14 (EC 3.4.19.-)protein27841% helix, 14% strandO00487
d26S proteasome non-ATPase regulatory subunit 8protein25761% helix, 3% strandP48556
eSem1protein4055% helix, 0% strand—
A26S protease regulatory subunit 7protein36140% helix, 11% strandP35998
B26S protease regulatory subunit 4protein34834% helix, 11% strandP62191
C26S protease regulatory subunit 8protein38444% helix, 10% strandP62195
D26S protease regulatory subunit 6Bprotein38039% helix, 14% strandP43686
E26S protease regulatory subunit 10Bprotein35340% helix, 11% strandP62333
F26S protease regulatory subunit 6Aprotein36639% helix, 11% strandP17980
G, gProteasome subunit alpha type-6 (EC 3.4.25.1)protein24035% helix, 22% strandP60900
H, hProteasome subunit alpha type-2 (EC 3.4.25.1)protein23232% helix, 25% strandP25787
I, iProteasome subunit alpha type-4 (EC 3.4.25.1)protein25038% helix, 18% strandP25789
J, jProteasome subunit alpha type-7 (EC 3.4.25.1)protein23934% helix, 17% strandO14818
K, kProteasome subunit alpha type-5 (EC 3.4.25.1)protein22832% helix, 15% strandP28066
L, lProteasome subunit alpha type-1 (EC 3.4.25.1)protein23828% helix, 19% strandP25786
M, mProteasome subunit alpha type-3 (EC 3.4.25.1)protein24030% helix, 24% strandP25788
N, nProteasome subunit beta type-6 (EC 3.4.25.1)protein19135% helix, 27% strandP28072
O, oProteasome subunit beta type-7 (EC 3.4.25.1)protein22028% helix, 31% strandQ99436
P, pProteasome subunit beta type-3 (EC 3.4.25.1)protein20428% helix, 28% strandP49720
Q, qProteasome subunit beta type-2 (EC 3.4.25.1)protein19931% helix, 21% strandP49721
R, rProteasome subunit beta type-5 (EC 3.4.25.1)protein20135% helix, 30% strandP28074
S, sProteasome subunit beta type-1 (EC 3.4.25.1)protein21332% helix, 26% strandP20618
T, tProteasome subunit beta type-4 (EC 3.4.25.1)protein21532% helix, 30% strandP28070
f26S proteasome non-ATPase regulatory subunit 2protein68961% helix, 0% strandQ13200

Ligands and binding sites

  • ZN · Zinc ion · metal · chains c

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

20 pockets found on a 1 Å grid, 20 with a druggability of 0.5 or more.

PocketVolume (ų)DruggabilityBuriednessLining residuesInside
111870.870.88135empty
210880.860.87135empty
38100.860.89119empty
411330.850.86139empty
57140.850.8983empty

Interfaces

155 interfaces between chains.

  • Z–c · 3948 Ų buried · 22 hydrogen bonds · protein-protein
  • E–F · 3858 Ų buried · 38 hydrogen bonds · protein-protein
  • C–D · 3392 Ų buried · 31 hydrogen bonds · protein-protein
  • A–B · 3159 Ų buried · 45 hydrogen bonds · protein-protein
  • A–F · 2942 Ų buried · 29 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 2 disulfide (disulfide).

Compared structures

  • P28070 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-4 (P28070) · a predicted model of the same protein · chain T against A, TM-score 0.99
  • P20618 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-1 (P20618) · a predicted model of the same protein · chain S against A, TM-score 0.99
  • P28072 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-6 (P28072) · a predicted model of the same protein · chain N against A, TM-score 0.99
  • P28074 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-5 (P28074) · a predicted model of the same protein · chain R against A, TM-score 0.98
  • P25786 · AlphaFold monomer V2.0 prediction for proteasome subunit alpha type-1 (P25786) · a predicted model of the same protein · chain L against A, TM-score 0.98
  • P49720 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-3 (P49720) · a predicted model of the same protein · chain P against A, TM-score 0.98
  • Q99436 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-7 (Q99436) · a predicted model of the same protein · chain O against A, TM-score 0.98
  • P49721 · AlphaFold monomer V2.0 prediction for proteasome subunit beta type-2 (P49721) · a predicted model of the same protein · chain Q against A, TM-score 0.98
  • P60900 · AlphaFold monomer V2.0 prediction for proteasome subunit alpha type-6 (P60900) · a predicted model of the same protein · chain G against A, TM-score 0.97
  • P25788 · AlphaFold monomer V2.0 prediction for proteasome subunit alpha type-3 (P25788) · a predicted model of the same protein · chain M against A, TM-score 0.96
  • P25789 · AlphaFold monomer V2.0 prediction for proteasome subunit alpha type-4 (P25789) · a predicted model of the same protein · chain I against A, TM-score 0.96
  • P28066 · AlphaFold monomer V2.0 prediction for proteasome subunit alpha type-5 (P28066) · a predicted model of the same protein · chain K against A, TM-score 0.95

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