+
Open data
-
Basic information
Entry | Database: PDB / ID: 6epf | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Ground state 26S proteasome (GS1) | |||||||||||||||
![]() |
| |||||||||||||||
![]() | ![]() ![]() | |||||||||||||||
Function / homology | ![]() nuclear proteasome complex / Cross-presentation of soluble exogenous antigens (endosomes) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of ornithine decarboxylase (ODC) / Metalloprotease DUBs / Assembly of the pre-replicative complex / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C ...nuclear proteasome complex / Cross-presentation of soluble exogenous antigens (endosomes) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of ornithine decarboxylase (ODC) / Metalloprotease DUBs / Assembly of the pre-replicative complex / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / UCH proteinases / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / The role of GTSE1 in G2/M progression after G2 checkpoint / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX3 expression and activity / GLI3 is processed to GLI3R by the proteasome / Activation of NF-kappaB in B cells / Degradation of beta-catenin by the destruction complex / Degradation of AXIN / Regulation of RAS by GAPs / Orc1 removal from chromatin / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() | |||||||||||||||
![]() | Guo, Q. / Lehmer, C. / Martinez-Sanchez, A. / Rudack, T. / Beck, F. / Hartmann, H. / Hipp, M.S. / Hartl, F.U. / Edbauer, D. / Baumeister, W. / Fernandez-Busnadiego, R. | |||||||||||||||
Funding support | ![]() ![]()
| |||||||||||||||
![]() | ![]() Title: In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment. Authors: Qiang Guo / Carina Lehmer / Antonio Martínez-Sánchez / Till Rudack / Florian Beck / Hannelore Hartmann / Manuela Pérez-Berlanga / Frédéric Frottin / Mark S Hipp / F Ulrich Hartl / ...Authors: Qiang Guo / Carina Lehmer / Antonio Martínez-Sánchez / Till Rudack / Florian Beck / Hannelore Hartmann / Manuela Pérez-Berlanga / Frédéric Frottin / Mark S Hipp / F Ulrich Hartl / Dieter Edbauer / Wolfgang Baumeister / Rubén 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- ...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. | |||||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 1.8 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 1.4 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 3916MC ![]() 3913C ![]() 3914C ![]() 3915C ![]() 3917C ![]() 4191C ![]() 6epcC ![]() 6epdC ![]() 6epeC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Proteasome subunit alpha type- ... , 7 types, 7 molecules ABCDEFG
#1: Protein | ![]() Mass: 27432.459 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P60901, ![]() |
---|---|
#2: Protein | ![]() Mass: 25955.549 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P17220, ![]() |
#3: Protein | ![]() Mass: 29539.830 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P21670, ![]() |
#4: Protein | ![]() Mass: 28369.439 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P48004, ![]() |
#5: Protein | ![]() Mass: 26416.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P34064, ![]() |
#6: Protein | ![]() Mass: 29557.541 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P18420, ![]() |
#7: Protein | ![]() Mass: 28456.275 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P18422, ![]() |
-Proteasome subunit beta type- ... , 7 types, 7 molecules 1234567
#8: Protein | ![]() Mass: 25309.576 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P28073, ![]() |
---|---|
#9: Protein | ![]() Mass: 29963.461 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: Q9JHW0, ![]() |
#10: Protein | ![]() Mass: 22988.895 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P40112, ![]() |
#11: Protein | ![]() Mass: 22941.381 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P40307, ![]() |
#12: Protein | ![]() Mass: 28615.408 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P28075, ![]() |
#13: Protein | ![]() Mass: 26511.301 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P18421, ![]() |
#14: Protein | ![]() Mass: 29226.248 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() References: UniProt: P34067, ![]() |
-Protein , 2 types, 2 molecules WY
#15: Protein | ![]() Mass: 40775.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
---|---|
#18: Protein | Mass: 8284.611 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
-Proteasome (Prosome, macropain) 26S subunit, non-ATPase, ... , 5 types, 5 molecules VSPRU
#16: Protein | Mass: 34620.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
---|---|
#21: Protein | Mass: 60778.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#22: Protein | Mass: 53011.246 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#24: Protein | Mass: 45658.398 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#25: Protein | Mass: 36551.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
-Proteasome 26S subunit, ... , 2 types, 2 molecules TL
#17: Protein | Mass: 39932.082 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
---|---|
#30: Protein | Mass: 45867.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
-26S proteasome non-ATPase regulatory subunit ... , 4 types, 4 molecules ZNQO
#19: Protein | Mass: 100300.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
---|---|
#20: Protein | Mass: 105870.117 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#23: Protein | Mass: 47526.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#26: Protein | Mass: 42867.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
-26S proteasome regulatory subunit ... , 5 types, 5 molecules HIKMJ
#27: Protein | Mass: 48640.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
---|---|
#28: Protein | Mass: 49260.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#29: Protein | Mass: 47468.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#31: Protein | Mass: 49611.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#32: Protein | Mass: 45694.047 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: CELL / 3D reconstruction method: subtomogram averaging |
-
Sample preparation
Component | Name: Ground state 26S proteasome (GS1) / Type: COMPLEX Details: in situ proteasome structure generated by subtomogram averaging Entity ID: all / Source: NATURAL |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Details: The grid was coated with C prior to use / Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1 |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 298 K |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2.4 sec. / Electron dose: 1.8 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
Image scans | Width: 3838 / Height: 3710 |
-
Processing
EM software |
| ||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 11.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7393 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
EM volume selection | Method: Template matching / Num. of tomograms: 9 / Num. of volumes extracted: 10367 / Reference model: average of manual picked subtomograms | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT |