[English] 日本語
Yorodumi
- EMDB-44926: Thermoplasma acidophilum 20S proteasome - alphaV24Y -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-44926
TitleThermoplasma acidophilum 20S proteasome - alphaV24Y
Map data
Sample
  • Complex: Thermoplasma acidophilum 20S proteasome alphaV24Y
    • Protein or peptide: Proteasome subunit alpha
    • Protein or peptide: Proteasome subunit beta
  • Ligand: water
KeywordsProtease / threonine protease / endopeptidase activity / HYDROLASE
Function / homology
Function and homology information


proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / proteasomal protein catabolic process / ubiquitin-dependent protein catabolic process / endopeptidase activity / cytoplasm
Similarity search - Function
Peptidase T1A, proteasome beta-subunit, archaeal / Proteasome alpha subunit, archaeal / Proteasome beta-type subunits signature. / Peptidase T1A, proteasome beta-subunit / Proteasome beta-type subunit, conserved site / Proteasome subunit A N-terminal signature / Proteasome alpha-type subunits signature. / Proteasome alpha-subunit, N-terminal domain / Proteasome subunit A N-terminal signature Add an annotation / Proteasome B-type subunit ...Peptidase T1A, proteasome beta-subunit, archaeal / Proteasome alpha subunit, archaeal / Proteasome beta-type subunits signature. / Peptidase T1A, proteasome beta-subunit / Proteasome beta-type subunit, conserved site / Proteasome subunit A N-terminal signature / Proteasome alpha-type subunits signature. / Proteasome alpha-subunit, N-terminal domain / Proteasome subunit A N-terminal signature Add an annotation / Proteasome B-type subunit / Proteasome beta-type subunit profile. / : / Proteasome alpha-type subunit / Proteasome alpha-type subunit profile. / Proteasome subunit / Proteasome, subunit alpha/beta / Nucleophile aminohydrolases, N-terminal
Similarity search - Domain/homology
Proteasome subunit alpha / Proteasome subunit beta
Similarity search - Component
Biological speciesThermoplasma acidophilum (acidophilic)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.38 Å
AuthorsChuah J / Smith D
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01AG064188 United States
CitationJournal: bioRxiv / Year: 2025
Title: Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes.
Authors: Janelle J Y Chuah / Madalena R Daugherty / David M Smith /
Abstract: Enhancing proteasome function has been a long-standing but challenging target of interest for the potential treatment of neurodegenerative diseases, emphasizing the importance of understanding ...Enhancing proteasome function has been a long-standing but challenging target of interest for the potential treatment of neurodegenerative diseases, emphasizing the importance of understanding proteasome activation mechanisms. Most proteasome activator complexes use the C-terminal HbYX (hydrophobic-tyrosine-almost any residue) motif to bind and trigger gate-opening in the 20S proteasome. This study defines a critical molecular interaction in the HbYX mechanism that triggers gate opening. We focus on the Hb site interaction and find it plays a surprisingly central and crucial role in driving the allosteric conformational changes that induce gate opening in the archaeal 20S. We examined the cryo-EM structure of two mutant archaeal proteasomes, αV24Y T20S and αV24F T20S. These two mutants were engineered to place a bulky aromatic residue in the HbYX hydrophobic pocket; both mutants are highly active, though their mechanisms of activation are undefined. Collectively, our findings indicate that the interaction between the Hb group of the HbYX motif and its corresponding hydrophobic pocket is sufficient to induce gate opening in a mechanistically similar way to the HbYX motif. The activation mechanism studied here involves the expansion of the hydrophobic binding site, allosterically altering the state of the IT switch thus triggering gate-opening. Furthermore, we show that the canonical αK66 residue, previously understood to be critical for proteasome activator binding, also plays a key role in stabilizing the open gate, irrespective of activator binding. This study differentiates between the residues in the HbYX motif that support binding interactions ("YX") versus those that allosterically contribute to gate opening ("Hb"). The insights reported here will guide future drug development efforts, particularly in designing small molecule proteasome activators, by targeting the identified hydrophobic pocket.
History
DepositionMay 18, 2024-
Header (metadata) releaseOct 30, 2024-
Map releaseOct 30, 2024-
UpdateApr 16, 2025-
Current statusApr 16, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_44926.png

Downloads & links

-
Map

FileDownload / File: emd_44926.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.54 Å/pix.
x 512 pix.
= 276.48 Å		0.54 Å/pix.
x 512 pix.
= 276.48 Å		0.54 Å/pix.
x 512 pix.
= 276.48 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.54 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.032
Minimum - Maximum-0.07042432 - 0.1863418
Average (Standard dev.)0.0006470988 (±0.009383919)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 276.48 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_44926_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_44926_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Thermoplasma acidophilum 20S proteasome alphaV24Y

EntireName: Thermoplasma acidophilum 20S proteasome alphaV24Y
Components
  • Complex: Thermoplasma acidophilum 20S proteasome alphaV24Y
    • Protein or peptide: Proteasome subunit alpha
    • Protein or peptide: Proteasome subunit beta
  • Ligand: water

-
Supramolecule #1: Thermoplasma acidophilum 20S proteasome alphaV24Y

SupramoleculeName: Thermoplasma acidophilum 20S proteasome alphaV24Y / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Thermoplasma acidophilum (acidophilic)
Molecular weightTheoretical: 700 kDa/nm

-
Macromolecule #1: Proteasome subunit alpha

MacromoleculeName: Proteasome subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 14 / Enantiomer: LEVO
Source (natural)Organism: Thermoplasma acidophilum (acidophilic)
Molecular weightTheoretical: 25.89349 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MQQGQMAYDR AITVFSPDGR LFQYEYAREA VKKGSTALGM KFANGVLLIS DKKVRSRLIE QNSIEKIQLI DDYVAAVTSG LVADARVLV DFARISAQQE KVTYGSLVNI ENLVKRVADQ MQQYTQYGGV RPYGVSLIFA GIDQIGPRLF DCDPAGTINE Y KATAIGSG ...String:
MQQGQMAYDR AITVFSPDGR LFQYEYAREA VKKGSTALGM KFANGVLLIS DKKVRSRLIE QNSIEKIQLI DDYVAAVTSG LVADARVLV DFARISAQQE KVTYGSLVNI ENLVKRVADQ MQQYTQYGGV RPYGVSLIFA GIDQIGPRLF DCDPAGTINE Y KATAIGSG KDAVVSFLER EYKENLPEKE AVTLGIKALK SSLEEGEELK APEIASITVG NKYRIYDQEE VKKFL

UniProtKB: Proteasome subunit alpha

-
Macromolecule #2: Proteasome subunit beta

MacromoleculeName: Proteasome subunit beta / type: protein_or_peptide / ID: 2 / Number of copies: 14 / Enantiomer: LEVO / EC number: proteasome endopeptidase complex
Source (natural)Organism: Thermoplasma acidophilum (acidophilic)
Molecular weightTheoretical: 23.169811 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MNQTLETGTT TVGITLKDAV IMATERRVTM ENFIMHKNGK KLFQIDTYTG MTIAGLVGDA QVLVRYMKAE LELYRLQRRV NMPIEAVAT LLSNMLNQVK YMPYMVQLLV GGIDTAPHVF SIDAAGGSVE DIYASTGSGS PFVYGVLESQ YSEKMTVDEG V DLVIRAIS ...String:
MNQTLETGTT TVGITLKDAV IMATERRVTM ENFIMHKNGK KLFQIDTYTG MTIAGLVGDA QVLVRYMKAE LELYRLQRRV NMPIEAVAT LLSNMLNQVK YMPYMVQLLV GGIDTAPHVF SIDAAGGSVE DIYASTGSGS PFVYGVLESQ YSEKMTVDEG V DLVIRAIS AAKQRDSASG GMIDVAVITR KDGYVQLPTD QIESRIRKLG LIL

UniProtKB: Proteasome subunit beta

-
Macromolecule #3: water

MacromoleculeName: water / type: ligand / ID: 3 / Number of copies: 396 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1 mg/mL
BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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

+
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8f7k

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.38 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 396542
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

-
Atomic model buiding 1

RefinementProtocol: FLEXIBLE FIT
Output model

PDB-9buz:
Thermoplasma acidophilum 20S proteasome - alphaV24Y

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more