PDBsum entry 6epe

Hydrolase

PDB id: 6epe

Contents

Protein chains

246 a.a.

234 a.a.

249 a.a.

246 a.a.

233 a.a.

238 a.a.

245 a.a.

202 a.a.

219 a.a.

205 a.a.

196 a.a.

201 a.a.

213 a.a.

216 a.a.

195 a.a.

289 a.a.

263 a.a.

24 a.a.

896 a.a.

905 a.a.

476 a.a.

456 a.a.

422 a.a.

389 a.a.

288 a.a.

376 a.a.

396 a.a.

385 a.a.

391 a.a.

389 a.a.

415 a.a.

406 a.a.

PDB id:

6epe

Name:

Hydrolase

Title:

Substrate processing state 26s proteasome (sps2)

Structure:

Proteasome subunit alpha type-6. Chain: a. Synonym: macropain iota chain,multicatalytic endopeptidase complex iota chain,proteasome iota chain. Proteasome subunit alpha type-2. Chain: b. Synonym: macropain subunit c3,multicatalytic endopeptidase complex subunit c3,proteasome component c3. Proteasome subunit alpha type-4.

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Norway rat. Organism_taxid: 10116

Authors:

Q.Guo,C.Lehmer,A.Martinez-Sanchez,T.Rudack,F.Beck,H.Hartmann, M.S.Hipp,F.U.Hartl,D.Edbauer,W.Baumeister,R.Fernandez-Busnadiego

Key ref:

Q.Guo et al. (2018). In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment. Cell, 172, 696. PubMed id: 29398115 DOI: 10.1016/j.cell.2017.12.030

Date:

11-Oct-17 Release date: 07-Feb-18

Protein chain

P60901  (PSA6_RAT) -  Proteasome subunit alpha type-6 from Rattus norvegicus

Seq: 246 a.a.

Struc: 246 a.a.

Protein chain

P17220  (PSA2_RAT) -  Proteasome subunit alpha type-2 from Rattus norvegicus

Seq: 234 a.a.

Struc: 234 a.a.

Protein chain

P21670  (PSA4_RAT) -  Proteasome subunit alpha type-4 from Rattus norvegicus

Seq: 261 a.a.

Struc: 249 a.a.

Protein chain

P48004  (PSA7_RAT) -  Proteasome subunit alpha type-7 from Rattus norvegicus

Seq: 254 a.a.

Struc: 246 a.a.

Protein chain

P34064  (PSA5_RAT) -  Proteasome subunit alpha type-5 from Rattus norvegicus

Seq: 241 a.a.

Struc: 233 a.a.

Protein chain

P18420  (PSA1_RAT) -  Proteasome subunit alpha type-1 from Rattus norvegicus

Seq: 263 a.a.

Struc: 238 a.a.

Protein chain

P18422  (PSA3_RAT) -  Proteasome subunit alpha type-3 from Rattus norvegicus

Seq: 255 a.a.

Struc: 245 a.a.

Protein chain

P28073  (PSB6_RAT) -  Proteasome subunit beta type-6 from Rattus norvegicus

Seq: 238 a.a.

Struc: 202 a.a.

Protein chain

Q9JHW0  (PSB7_RAT) -  Proteasome subunit beta type-7 from Rattus norvegicus

Seq: 277 a.a.

Struc: 219 a.a.

Protein chain

P40112  (PSB3_RAT) -  Proteasome subunit beta type-3 from Rattus norvegicus

Seq: 205 a.a.

Struc: 205 a.a.

Protein chain

P40307  (PSB2_RAT) -  Proteasome subunit beta type-2 from Rattus norvegicus

Seq: 201 a.a.

Struc: 196 a.a.

Protein chain

P28075  (PSB5_RAT) -  Proteasome subunit beta type-5 from Rattus norvegicus

Seq: 263 a.a.

Struc: 201 a.a.

Protein chain

P18421  (PSB1_RAT) -  Proteasome subunit beta type-1 from Rattus norvegicus

Seq: 240 a.a.

Struc: 213 a.a.

Protein chain

P34067  (PSB4_RAT) -  Proteasome subunit beta type-4 from Rattus norvegicus

Seq: 263 a.a.

Struc: 216 a.a.

Protein chain

Q9ESH1  (Q9ESH1_RAT) -  26S proteasome non-ATPase regulatory subunit 4 from Rattus norvegicus

Seq: 377 a.a.

Struc: 195 a.a.

Protein chain

Q4V8E2  (Q4V8E2_RAT) -  Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 14 from Rattus norvegicus

Seq: 310 a.a.

Struc: 289 a.a.

Protein chain

F1LMQ3  (F1LMQ3_RAT) -  26S proteasome non-ATPase regulatory subunit 8 from Rattus norvegicus

Seq: 353 a.a.

Struc: 263 a.a.

Protein chain

D3ZHW9  (D3ZHW9_RAT) -  26S proteasome complex subunit SEM1 from Rattus norvegicus

Seq: 70 a.a.

Struc: 24 a.a.

Protein chain

Q4FZT9  (PSMD2_RAT) -  26S proteasome non-ATPase regulatory subunit 2 from Rattus norvegicus

Seq: 908 a.a.

Struc: 896 a.a.

Protein chain

O88761  (PSMD1_RAT) -  26S proteasome non-ATPase regulatory subunit 1 from Rattus norvegicus

Seq: 953 a.a.

Struc: 905 a.a.

Protein chain

A6HIT6  (A6HIT6_RAT) -  Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 3 from Rattus norvegicus

Seq: 530 a.a.

Struc: 476 a.a.

Protein chain

Q5XIC6  (Q5XIC6_RAT) -  Proteasome (Prosome, macropain) 26S subunit, non-ATPase, 12 from Rattus norvegicus

Seq: 456 a.a.

Struc: 456 a.a.

Protein chain

F1LMZ8  (PSD11_RAT) -  26S proteasome non-ATPase regulatory subunit 11 from Rattus norvegicus

Seq: 422 a.a.

Struc: 422 a.a.

Protein chain

Q6PCT9  (Q6PCT9_RAT) -  26S proteasome non-ATPase regulatory subunit 6 from Rattus norvegicus

Seq: 389 a.a.

Struc: 389 a.a.

Protein chain

D4AEH3  (D4AEH3_RAT) -  Proteasome 26S subunit, non-ATPase 7 from Rattus norvegicus

Seq: 314 a.a.

Struc: 288 a.a.*

Protein chain

B0BN93  (PSD13_RAT) -  26S proteasome non-ATPase regulatory subunit 13 from Rattus norvegicus

Seq: 376 a.a.

Struc: 376 a.a.

Protein chain

Q63347  (PRS7_RAT) -  26S proteasome regulatory subunit 7 from Rattus norvegicus

Seq: 433 a.a.

Struc: 396 a.a.

Protein chain

P62193  (PRS4_RAT) -  26S proteasome regulatory subunit 4 from Rattus norvegicus

Seq: 440 a.a.

Struc: 385 a.a.

Protein chain

Q63570  (PRS6B_RAT) -  26S proteasome regulatory subunit 6B from Rattus norvegicus

Seq: 418 a.a.

Struc: 391 a.a.

Protein chain

G3V6W6  (G3V6W6_RAT) -  Proteasome 26S subunit, ATPase 6 from Rattus norvegicus

Seq: 403 a.a.

Struc: 389 a.a.

Protein chain

Q63569  (PRS6A_RAT) -  26S proteasome regulatory subunit 6A from Rattus norvegicus

Seq: 439 a.a.

Struc: 415 a.a.

Protein chain

P62198  (PRS8_RAT) -  26S proteasome regulatory subunit 8 from Rattus norvegicus

Seq: 406 a.a.

Struc: 406 a.a.

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, 1, 2, 3, 4, 5, 6, 7: E.C.3.4.25.1 - proteasome endopeptidase complex.
• Reaction: Cleavage at peptide bonds with very broad specificity.

DOI no: 10.1016/j.cell.2017.12.030

Cell 172:696 (2018)

PubMed id: 29398115

In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment.

Q.Guo, C.Lehmer, A.Martínez-Sánchez, T.Rudack, F.Beck, H.Hartmann, M.Pérez-Berlanga, F.Frottin, M.S.Hipp, F.U.Hartl, D.Edbauer, W.Baumeister, R.Fernández-Busnadiego.

ABSTRACT

Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo-electron tomography to dissect the molecular architecture of protein aggregates within intact neurons at high resolution. We focus on the poly-Gly-Ala (poly-GA) aggregates resulting from aberrant translation of an expanded GGGGCC repeat in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. We find that poly-GA aggregates consist of densely packed twisted ribbons that recruit numerous 26S proteasome complexes, while other macromolecules are largely excluded. Proximity to poly-GA ribbons stabilizes a transient substrate-processing conformation of the 26S proteasome, suggesting stalled degradation. Thus, poly-GA aggregates may compromise neuronal proteostasis by driving the accumulation and functional impairment of a large fraction of cellular proteasomes.