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- EMDB-28906: Thermoplasma acidophilum 20S proteasome - wild type bound to ZYA -
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Open data
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Basic information
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Title | Thermoplasma acidophilum 20S proteasome - wild type bound to ZYA | |||||||||
![]() | T20S ZYA EM Map unsharpened | |||||||||
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![]() | Protease / threonine protease / endopeptidase activity / HYDROLASE | |||||||||
Function / homology | ![]() proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / proteasomal protein catabolic process / threonine-type endopeptidase activity / ubiquitin-dependent protein catabolic process / endopeptidase activity / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 1.94 Å | |||||||||
![]() | Chuah J / Smith D | |||||||||
Funding support | ![]()
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![]() | ![]() Title: High resolution structures define divergent and convergent mechanisms of archaeal proteasome activation. Authors: Janelle J Y Chuah / Matthew S Rexroad / David M Smith / ![]() Abstract: Considering the link between neurodegenerative diseases and impaired proteasome function, and the neuro-protective impact of enhanced proteasome activity in animal models, it's crucial to understand ...Considering the link between neurodegenerative diseases and impaired proteasome function, and the neuro-protective impact of enhanced proteasome activity in animal models, it's crucial to understand proteasome activation mechanisms. A hydrophobic-tyrosine-any residue (HbYX) motif on the C-termini of proteasome-activating complexes independently triggers gate-opening of the 20S core particle for protein degradation; however, the causal allosteric mechanism remains unclear. Our study employs a structurally irreducible dipeptide HbYX mimetic to investigate the allosteric mechanism of gate-opening in the archaeal proteasome. High-resolution cryo-EM structures pinpoint vital residues and conformational changes in the proteasome α-subunit implicated in HbYX-dependent activation. Using point mutations, we simulated the HbYX-bound state, providing support for our mechanistic model. We discerned four main mechanistic elements triggering gate-opening: 1) back-loop rearrangement adjacent to K66, 2) intra- and inter- α subunit conformational changes, 3) occupancy of the hydrophobic pocket, and 4) a highly conserved isoleucine-threonine pair in the 20S channel stabilizing the open and closed states, termed the "IT switch." Comparison of different complexes unveiled convergent and divergent mechanism of 20S gate-opening among HbYX-dependent and independent activators. This study delivers a detailed molecular model for HbYX-dependent 20S gate-opening, enabling the development of small molecule proteasome activators that hold promise to treat neurodegenerative diseases. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 163.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.5 KB 17.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.4 KB | Display | ![]() |
Images | ![]() | 49.7 KB | ||
Others | ![]() ![]() ![]() | 33 MB 301.7 MB 301.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8f7kMC ![]() 8f66C ![]() 8f6aC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | T20S ZYA EM Map unsharpened | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.73636 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: T20S ZYA Denmod Map
File | emd_28906_additional_1.map | ||||||||||||
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Annotation | T20S ZYA Denmod Map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: T20S ZYA EM Map Half A
File | emd_28906_half_map_1.map | ||||||||||||
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Annotation | T20S ZYA EM Map Half A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: T20S ZYA EM Map Half B
File | emd_28906_half_map_2.map | ||||||||||||
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Annotation | T20S ZYA EM Map Half B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Wild-type Thermoplasma acidophilum 20S proteasome bound to ZYA
Entire | Name: Wild-type Thermoplasma acidophilum 20S proteasome bound to ZYA |
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Components |
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-Supramolecule #1: Wild-type Thermoplasma acidophilum 20S proteasome bound to ZYA
Supramolecule | Name: Wild-type Thermoplasma acidophilum 20S proteasome bound to ZYA type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2, #1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 700 kDa/nm |
-Macromolecule #1: Proteasome subunit alpha
Macromolecule | Name: Proteasome subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 14 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.441996 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GQMAYDRAIT VFSPDGRLFQ VEYAREAVKK GSTALGMKFA NGVLLISDKK VRSRLIEQNS IEKIQLIDDY VAAVTSGLVA DARVLVDFA RISAQQEKVT YGSLVNIENL VKRVADQMQQ YTQYGGVRPY GVSLIFAGID QIGPRLFDCD PAGTINEYKA T AIGSGKDA ...String: GQMAYDRAIT VFSPDGRLFQ VEYAREAVKK GSTALGMKFA NGVLLISDKK VRSRLIEQNS IEKIQLIDDY VAAVTSGLVA DARVLVDFA RISAQQEKVT YGSLVNIENL VKRVADQMQQ YTQYGGVRPY GVSLIFAGID QIGPRLFDCD PAGTINEYKA T AIGSGKDA VVSFLEREYK ENLPEKEAVT LGIKALKSSL EEGEELKAPE IASITVGNKY RIYDQEEVKK FL UniProtKB: Proteasome subunit alpha |
-Macromolecule #2: Proteasome subunit beta
Macromolecule | Name: Proteasome subunit beta / type: protein_or_peptide / ID: 2 / Number of copies: 14 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.294848 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: TTTVGITLKD AVIMATERRV TMENFIMHKN GKKLFQIDTY TGMTIAGLVG DAQVLVRYMK AELELYRLQR RVNMPIEAVA TLLSNMLNQ VKYMPYMVQL LVGGIDTAPH VFSIDAAGGS VEDIYASTGS GSPFVYGVLE SQYSEKMTVD EGVDLVIRAI S AAKQRDSA ...String: TTTVGITLKD AVIMATERRV TMENFIMHKN GKKLFQIDTY TGMTIAGLVG DAQVLVRYMK AELELYRLQR RVNMPIEAVA TLLSNMLNQ VKYMPYMVQL LVGGIDTAPH VFSIDAAGGS VEDIYASTGS GSPFVYGVLE SQYSEKMTVD EGVDLVIRAI S AAKQRDSA SGGMIDVAVI TRKDGYVQLP TDQIESRIRK LGLIL UniProtKB: Proteasome subunit beta |
-Macromolecule #3: N-[(benzyloxy)carbonyl]-L-tyrosyl-D-alanine
Macromolecule | Name: N-[(benzyloxy)carbonyl]-L-tyrosyl-D-alanine / type: ligand / ID: 3 / Number of copies: 14 / Formula: XIB |
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Molecular weight | Theoretical: 386.398 Da |
Chemical component information | ![]() ChemComp-XIB: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | ![]() PDB-8f7k: |