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- PDB-9ceg: 20S Proteasome core particle beta-T1A mutant resting state (Frame 20) -

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Basic information

Entry
Database: PDB / ID: 9ceg
Title20S Proteasome core particle beta-T1A mutant resting state (Frame 20)
Components
  • Proteasome subunit alpha
  • Proteasome subunit beta
KeywordsANTIMICROBIAL PROTEIN / Proteasome / Proteolysis
Function / homology
Function and homology information


symbiont-mediated perturbation of host defenses / zymogen binding / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / proteasomal protein catabolic process / proteolysis involved in protein catabolic process / peptidoglycan-based cell wall / modification-dependent protein catabolic process ...symbiont-mediated perturbation of host defenses / zymogen binding / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / proteasomal protein catabolic process / proteolysis involved in protein catabolic process / peptidoglycan-based cell wall / modification-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / extracellular region / plasma membrane / cytoplasm
Similarity search - Function
Proteasome, alpha subunit, bacterial / Proteasome subunit beta, actinobacteria / 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 beta / Proteasome subunit alpha
Similarity search - Component
Biological speciesMycobacterium tuberculosis (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.86 Å
AuthorsZeytuni, N. / Uday, A.B. / Vahidi, S. / Turner, M.
Funding support Canada, 2items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR)PJT451412 Canada
Natural Sciences and Engineering Research Council (NSERC, Canada)RGPIN/03031-2022 Canada
CitationJournal: Nat Commun / Year: 2025
Title: Structural basis for allosteric modulation of M. tuberculosis proteasome core particle.
Authors: Madison Turner / Adwaith B Uday / Algirdas Velyvis / Enrico Rennella / Natalie Zeytuni / Siavash Vahidi /
Abstract: The Mycobacterium tuberculosis (Mtb) proteasome system selectively degrades damaged or misfolded proteins and is crucial for the pathogen's survival within the host. Targeting the 20S core particle ...The Mycobacterium tuberculosis (Mtb) proteasome system selectively degrades damaged or misfolded proteins and is crucial for the pathogen's survival within the host. Targeting the 20S core particle (CP) offers a viable strategy for developing tuberculosis treatments. The activity of Mtb 20S CP, like that of its eukaryotic counterpart, is allosterically regulated, yet the specific conformations involved have not been captured in high-resolution structures to date. Here, we use single-particle electron cryomicroscopy and H/D exchange mass spectrometry to determine the Mtb 20S CP structure in an auto-inhibited state that is distinguished from the canonical resting state by the conformation of switch helices at the α/β interface. The rearrangement of these helices collapses the S1 pocket, effectively inhibiting substrate binding. Biochemical experiments show that the Mtb 20S CP activity can be altered through allosteric sites far from the active site. Our findings underscore the potential of targeting allostery to develop antituberculosis therapeutics.
History
DepositionJun 26, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 12, 2025Provider: repository / Type: Initial release
Revision 1.1Apr 16, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Proteasome subunit alpha
B: Proteasome subunit alpha
C: Proteasome subunit alpha
D: Proteasome subunit alpha
E: Proteasome subunit alpha
F: Proteasome subunit alpha
G: Proteasome subunit alpha
H: Proteasome subunit alpha
I: Proteasome subunit alpha
J: Proteasome subunit alpha
K: Proteasome subunit alpha
L: Proteasome subunit alpha
M: Proteasome subunit alpha
N: Proteasome subunit alpha
O: Proteasome subunit beta
P: Proteasome subunit beta
Q: Proteasome subunit beta
R: Proteasome subunit beta
S: Proteasome subunit beta
T: Proteasome subunit beta
U: Proteasome subunit beta
V: Proteasome subunit beta
W: Proteasome subunit beta
X: Proteasome subunit beta
Y: Proteasome subunit beta
Z: Proteasome subunit beta
a: Proteasome subunit beta
b: Proteasome subunit beta


Theoretical massNumber of molelcules
Total (without water)718,57028
Polymers718,57028
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1chain "E"
d_2ens_1chain "B"
d_3ens_1chain "C"
d_4ens_1chain "D"
d_5ens_1chain "A"
d_6ens_1chain "F"
d_7ens_1chain "G"
d_8ens_1chain "H"
d_9ens_1chain "I"
d_10ens_1chain "J"
d_11ens_1chain "K"
d_12ens_1chain "L"
d_13ens_1chain "M"
d_14ens_1chain "N"
d_1ens_2chain "O"
d_2ens_2chain "P"
d_3ens_2chain "Q"
d_4ens_2chain "R"
d_5ens_2chain "S"
d_6ens_2chain "T"
d_7ens_2chain "U"
d_8ens_2chain "V"
d_9ens_2chain "W"
d_10ens_2chain "X"
d_11ens_2chain "Y"
d_12ens_2chain "Z"
d_13ens_2chain "a"
d_14ens_2chain "b"

NCS domain segments:

Component-ID: 1

Dom-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_1ens_1SERSERLEULEUEE8 - 2348 - 234
d_2ens_1SERSERLEULEUBB8 - 2348 - 234
d_3ens_1SERSERLEULEUCC8 - 2348 - 234
d_4ens_1SERSERLEULEUDD8 - 2348 - 234
d_5ens_1SERSERLEULEUAA8 - 2348 - 234
d_6ens_1SERSERLEULEUFF8 - 2348 - 234
d_7ens_1SERSERLEULEUGG8 - 2348 - 234
d_8ens_1SERSERLEULEUHH8 - 2348 - 234
d_9ens_1SERSERLEULEUII8 - 2348 - 234
d_10ens_1SERSERLEULEUJJ8 - 2348 - 234
d_11ens_1SERSERLEULEUKK8 - 2348 - 234
d_12ens_1SERSERLEULEULL8 - 2348 - 234
d_13ens_1SERSERLEULEUMM8 - 2348 - 234
d_14ens_1SERSERLEULEUNN8 - 2348 - 234
d_1ens_2ALAALASERSEROO1 - 2221 - 222
d_2ens_2ALAALASERSERPP1 - 2221 - 222
d_3ens_2ALAALASERSERQQ1 - 2221 - 222
d_4ens_2ALAALASERSERRR1 - 2221 - 222
d_5ens_2ALAALASERSERSS1 - 2221 - 222
d_6ens_2ALAALASERSERTT1 - 2221 - 222
d_7ens_2ALAALASERSERUU1 - 2221 - 222
d_8ens_2ALAALASERSERVV1 - 2221 - 222
d_9ens_2ALAALASERSERWW1 - 2221 - 222
d_10ens_2ALAALASERSERXX1 - 2221 - 222
d_11ens_2ALAALASERSERYY1 - 2221 - 222
d_12ens_2ALAALASERSERZZ1 - 2221 - 222
d_13ens_2ALAALASERSERaAA1 - 2221 - 222
d_14ens_2ALAALASERSERbBA1 - 2221 - 222

NCS ensembles :
ID
ens_1
ens_2

NCS oper:
IDCodeMatrixVector
1given(0.227482907625, -0.973782064955, 0.000129267205163), (-0.973775562944, -0.227481870119, -0.00362653845104), (0.00356086404707, 0.000699098265977, -0.999993415733)334.268232445, 422.455914892, 382.251598152
2given(-0.225257654361, 0.974296913735, -0.00212439122331), (-0.974297839951, -0.225260480479, -0.00119791558814), (-0.00164566684812, 0.00179995012458, 0.999997025976)48.7107428649, 421.485239037, -0.0991183821848
3given(0.621799726428, 0.783176246925, 0.000257810038035), (-0.783175669838, 0.621799614923, -0.00105311701711), (-0.000985082415405, 0.000452917323906, 0.999999412239)-77.5427603332, 222.682595868, 0.0421510778533
4given(-0.62296356073, -0.782250235703, 0.000985264511217), (-0.782250753931, 0.622963629167, -0.000273329813468), (-0.000399971644587, -0.000940998420573, -0.999999477272)460.350568391, 222.122034311, 383.428873694
5given(0.628080244677, -0.778136560974, 0.00432420191038), (0.778138687511, 0.628090580464, 0.00155104178175), (-0.00392291280592, 0.00239065009729, 0.999989447718)218.998587865, -78.0828588351, 0.276395720803
6given(-0.22109479216, -0.975252322601, 1.19071474754E-5), (0.975252322491, -0.221094792338, -1.66217060317E-5), (1.88429657114E-5, 7.93750058923E-6, 0.999999999791)420.530337376, 47.1268526942, -0.117170664895
7given(-0.900797237585, -0.434239938581, 0.000111801990552), (0.434239843201, -0.900797163084, -0.000479121604305), (0.000308764651942, -0.000383042538779, 0.999999878971)447.147206443, 280.980719055, -0.0540619302266
8given(-0.902106581026, 0.431499721712, -0.00342149556478), (-0.431498088077, -0.902112998585, -0.00124006838156), (-0.00362166478514, 0.000357694946634, 0.999993377777)282.518477464, 447.12503684, 0.609765636819
9given(-0.999982435319, -0.00458570998847, -0.00375503894487), (-0.00458083146076, 0.999988654108, -0.00130676662832), (0.00376098879338, -0.00128954247484, -0.999992095991)384.826432739, 1.38248903382, 382.572956907
10given(-0.624358148258, 0.781137105966, -0.00131315930561), (0.781137548196, 0.624358925114, 0.000251850878747), (0.00101661279911, -0.000868512892082, -0.999999106091)161.798130282, -77.6283809998, 383.084040711
11given(0.222249136443, 0.97498897252, -0.00135085696368), (0.974988966147, -0.222250634513, -0.00108228900418), (-0.00135544866147, -0.00107653283787, -0.999998501917)-37.4386383811, 47.6071558628, 383.610472599
12given(0.899730094726, 0.436445221293, 0.00115128436746), (0.436442272373, -0.899729690102, 0.00215119395773), (0.00197472305008, -0.00143302477788, -0.99999702345)-64.5887124139, 279.597702063, 382.995501047
13given(0.902015543793, -0.431701224828, -0.00141818123013), (-0.431701189126, -0.902016609006, 0.00034696355643), (-0.00142900761644, 0.000299264002414, -0.999998934189)101.75049047, 446.73645506, 383.361541031
14given(-0.622701442584, 0.782459441636, -0.000368236944556), (0.782459321093, 0.622701551219, 0.000434677181516), (0.000569418981332, -1.745632165E-5, -0.999999837729)161.074248643, -77.7079972959, 382.944104323
15given(-0.9999996132, 0.000647166068616, -0.000595631226163), (0.000647285339807, 0.999999770496, -0.000200072364536), (0.000595501609418, -0.000200457830509, -0.999999802597)383.100750167, -0.0857945925243, 382.980311779
16given(-0.622702635047, -0.782457962918, -0.00098212608952), (-0.782457798732, 0.622703296266, -0.000630891141461), (0.00110521895066, 0.000375614641867, -0.999999318702)460.820760424, 222.204193169, 382.786419344
17given(0.221994945432, -0.975047793741, 0.000210055114404), (-0.975047792049, -0.221994982859, -0.000175518202989), (0.000217769818107, -0.000165849621614, -0.999999962535)335.6407079, 420.85677364, 383.029969008
18given(0.900350080344, -0.435166225094, 0.000298934777374), (-0.435166266556, -0.900350105622, 8.80822974184E-5), (0.000230815517518, -0.000209391234571, -0.99999995144)102.257915668, 447.321348568, 383.031762774
19given(0.901594658096, 0.432581661878, 0.000422256178232), (0.432581453471, -0.901594715953, 0.000504259748855), (0.000598837459251, -0.000271977704544, -0.999999783711)-64.172050905, 281.255121307, 382.989625871
20given(0.222479664941, 0.974937029576, -0.000766191232988), (0.974936453766, -0.222478342094, 0.00151605326686), (0.00130759551343, -0.00108427878644, -0.999998557266)-37.6745590867, 47.1543114747, 382.972525533
21given(0.624273077335, 0.781206154313, 0.000263397215714), (-0.78120589008, 0.624273094925, -0.000678422471834), (-0.000694419605269, 0.000217753427879, 0.999999735182)-77.7136929001, 221.803821457, 0.0847918793725
22given(-0.221287912538, 0.975208507039, -0.00016602000173), (-0.975208477961, -0.221287848849, 0.000335358194835), (0.00029030595546, 0.000236114828086, 0.999999929986)47.1962709608, 420.740776717, -0.0923274229109
23given(-0.901051481884, 0.433710803898, -0.00107961911586), (-0.43371156786, -0.901051555907, 0.000607866792828), (-0.000709154088749, 0.0010159625739, 0.99999923246)281.217977017, 447.104138946, -0.0244611341611
24given(-0.901331328944, -0.433129051646, -0.00102960400534), (0.433128937908, -0.901331906569, 0.000342560661762), (-0.0010763879157, -0.000137190632788, 0.999999411284)447.311720009, 281.084328913, 0.206110666371
25given(-0.223763017264, -0.974642722562, -0.00129439636021), (0.974643064703, -0.22376406957, 0.000733208835379), (-0.00100425605272, -0.00109750941416, 0.999998893471)421.257549729, 47.4846433045, 0.342183162739
26given(0.622992493468, -0.782227190984, 0.000987302789651), (0.782227439462, 0.622992934119, 0.00019233076225), (-0.000765529013683, 0.000652474711978, 0.999999494121)221.823303925, -77.6978366477, 0.026365887883

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Components

#1: Protein
Proteasome subunit alpha / 20S proteasome alpha subunit / Proteasome core protein PrcA


Mass: 26911.039 Da / Num. of mol.: 14
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium tuberculosis (bacteria) / Gene: prcA, Rv2109c / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P9WHU1
#2: Protein
Proteasome subunit beta / 20S proteasome beta subunit / Proteasome core protein PrcB


Mass: 24415.357 Da / Num. of mol.: 14 / Mutation: T1A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium tuberculosis (bacteria) / Gene: prcB, Rv2110c / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P9WHT9, proteasome endopeptidase complex
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: 20S Proteasome core particle beta-T1A mutant ON state (Frame 20)
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Mycobacterium tuberculosis (bacteria)
Source (recombinant)Organism: Escherichia coli BL21(DE3) (bacteria)
Buffer solutionpH: 7.4
Buffer component
IDConc.NameFormulaBuffer-ID
1100 mMSodium chlorideNaCl1
250 mMSodium phosphate monobasicNaH2PO41
SpecimenConc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2750 nm / Nominal defocus min: 1250 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM software
IDNameVersionCategory
9PHENIXdev_5316model refinement
10cryoSPARC4initial Euler assignment
11cryoSPARC4final Euler assignment
13cryoSPARC43D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 2.86 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 147239
Details: The particles used are D7 symmetry expanded and the number of particles mentioned is after symmetry expansion.
Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 60.05 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.001546802
ELECTRON MICROSCOPYf_angle_d0.398763350
ELECTRON MICROSCOPYf_chiral_restr0.04157210
ELECTRON MICROSCOPYf_plane_restr0.00348358
ELECTRON MICROSCOPYf_dihedral_angle_d3.01466818
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2EEELECTRON MICROSCOPYNCS constraints2.48008602633E-13
ens_1d_3EEELECTRON MICROSCOPYNCS constraints1.60908688344E-12
ens_1d_4EEELECTRON MICROSCOPYNCS constraints7.31412977587E-13
ens_1d_5EEELECTRON MICROSCOPYNCS constraints2.83087538102E-13
ens_1d_6EEELECTRON MICROSCOPYNCS constraints3.18039469446E-13
ens_1d_7EEELECTRON MICROSCOPYNCS constraints2.78761923466E-10
ens_1d_8EEELECTRON MICROSCOPYNCS constraints2.01424662713E-13
ens_1d_9EEELECTRON MICROSCOPYNCS constraints1.64477700577E-12
ens_1d_10EEELECTRON MICROSCOPYNCS constraints3.24349826656E-13
ens_1d_11EEELECTRON MICROSCOPYNCS constraints1.40523299505E-10
ens_1d_12EEELECTRON MICROSCOPYNCS constraints3.6636967716E-13
ens_1d_13EEELECTRON MICROSCOPYNCS constraints9.13893351265E-13
ens_1d_14EEELECTRON MICROSCOPYNCS constraints1.08296877903E-11
ens_2d_2OOELECTRON MICROSCOPYNCS constraints1.23101704139E-13
ens_2d_3OOELECTRON MICROSCOPYNCS constraints3.55245655379E-13
ens_2d_4OOELECTRON MICROSCOPYNCS constraints5.46105713123E-12
ens_2d_5OOELECTRON MICROSCOPYNCS constraints2.60155445126E-13
ens_2d_6OOELECTRON MICROSCOPYNCS constraints4.72519058456E-11
ens_2d_7OOELECTRON MICROSCOPYNCS constraints5.88269106465E-13
ens_2d_8OOELECTRON MICROSCOPYNCS constraints1.354758558E-10
ens_2d_9OOELECTRON MICROSCOPYNCS constraints3.72830006415E-13
ens_2d_10OOELECTRON MICROSCOPYNCS constraints4.84482550574E-12
ens_2d_11OOELECTRON MICROSCOPYNCS constraints7.05190904253E-13
ens_2d_12OOELECTRON MICROSCOPYNCS constraints2.34386780507E-11
ens_2d_13OOELECTRON MICROSCOPYNCS constraints2.47989994967E-12
ens_2d_14OOELECTRON MICROSCOPYNCS constraints9.061361772E-11

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