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- PDB-6muv: The structure of the Plasmodium falciparum 20S proteasome in comp... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6muv | |||||||||
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Title | The structure of the Plasmodium falciparum 20S proteasome in complex with two PA28 activators | |||||||||
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Function / homology | ![]() proteasome activator complex / positive regulation of endopeptidase activity / regulation of G1/S transition of mitotic cell cycle / endopeptidase activator activity / proteasomal ubiquitin-independent protein catabolic process / proteasome core complex / ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Metcalfe, R.D. / Xie, S.C. / Hanssen, E. / Gillett, D.L. / Leis, A.P. / Tilley, L. / Griffin, M.D.W. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The structure of the PA28-20S proteasome complex from Plasmodium falciparum and implications for proteostasis. Authors: Stanley C Xie / Riley D Metcalfe / Eric Hanssen / Tuo Yang / David L Gillett / Andrew P Leis / Craig J Morton / Michael J Kuiper / Michael W Parker / Natalie J Spillman / Wilson Wong / ...Authors: Stanley C Xie / Riley D Metcalfe / Eric Hanssen / Tuo Yang / David L Gillett / Andrew P Leis / Craig J Morton / Michael J Kuiper / Michael W Parker / Natalie J Spillman / Wilson Wong / Christopher Tsu / Lawrence R Dick / Michael D W Griffin / Leann Tilley / ![]() ![]() Abstract: The activity of the proteasome 20S catalytic core is regulated by protein complexes that bind to one or both ends. The PA28 regulator stimulates 20S proteasome peptidase activity in vitro, but its ...The activity of the proteasome 20S catalytic core is regulated by protein complexes that bind to one or both ends. The PA28 regulator stimulates 20S proteasome peptidase activity in vitro, but its role in vivo remains unclear. Here, we show that genetic deletion of the PA28 regulator from Plasmodium falciparum (Pf) renders malaria parasites more sensitive to the antimalarial drug dihydroartemisinin, indicating that PA28 may play a role in protection against proteotoxic stress. The crystal structure of PfPA28 reveals a bell-shaped molecule with an inner pore that has a strong segregation of charges. Small-angle X-ray scattering shows that disordered loops, which are not resolved in the crystal structure, extend from the PfPA28 heptamer and surround the pore. Using single particle cryo-electron microscopy, we solved the structure of Pf20S in complex with one and two regulatory PfPA28 caps at resolutions of 3.9 and 3.8 Å, respectively. PfPA28 binds Pf20S asymmetrically, strongly engaging subunits on only one side of the core. PfPA28 undergoes rigid body motions relative to Pf20S. Molecular dynamics simulations support conformational flexibility and a leaky interface. We propose lateral transfer of short peptides through the dynamic interface as a mechanism facilitating the release of proteasome degradation products. | |||||||||
Validation Report | ![]() ![]() ![]() | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmcif format | ![]() ![]() ![]() |
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-Related structure data
Related structure data | ![]() 9257CM ![]() 9258C ![]() 9259C ![]() 6dfkC ![]() 6muwC ![]() 6muxC C: citing same article ( M: map data used to model this data |
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Similar-shape strucutres |
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Assembly
Deposited unit | ![]()
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Components
-20S proteasome alpha- ... , 7 types, 14 molecules AOBPCQDRESFTGU
#1: Protein | Mass: 29531.656 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IAR3, ![]() #2: Protein | Mass: 26556.391 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: C6KST3, ![]() #3: Protein | Mass: 27977.664 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IDG3, ![]() #4: Protein | Mass: 27263.285 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IDG2, ![]() #5: Protein | Mass: 28417.367 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IBI3, ![]() #6: Protein | Mass: 28871.697 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IK90, ![]() #7: Protein | Mass: 29324.295 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: O77396, ![]() |
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-20S proteasome beta- ... , 7 types, 14 molecules HVIWJXKYLZMaNb
#8: Protein | Mass: 29143.936 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8I0U7, ![]() #9: Protein | Mass: 25104.885 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8I6T3, ![]() #10: Protein | Mass: 24533.131 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8I261, ![]() #11: Protein | Mass: 22889.105 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IKC9, ![]() #12: Protein | Mass: 23620.646 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q8IJT1, ![]() #13: Protein | Mass: 27301.203 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: C0H4E8, ![]() #14: Protein | Mass: 30909.893 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() ![]() Strain: isolate 3D7 References: UniProt: Q7K6A9, ![]() |
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-Protein , 1 types, 14 molecules cdefghijklmnop
#15: Protein | Mass: 33178.773 Da / Num. of mol.: 14 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Strain: isolate 3D7 / Gene: PF3D7_0907700 / Production host: ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Molecular weight |
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() ![]() | ||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K / Details: wait time 0sec blot time 2sec blot force -1 |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10 sec. / Electron dose: 32 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5200 |
EM imaging optics | Energyfilter name![]() |
Image scans | Sampling size: 5 µm / Width: 3838 / Height: 3710 / Movie frames/image: 40 / Used frames/image: 1-40 |
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Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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Image processing | Details: Images were gain corrected | ||||||||||||||||||||||||||||||||||||||||||||||||||
CTF correction![]() | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 212749 Details: Relion autopick from 5 class averages resulting from 200o0 particle picked manually | ||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 27516 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 99.23 / Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6DFK Pdb chain-ID: M |