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- PDB-7ln4: Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and poly... -
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Basic information
Entry | Database: PDB / ID: 7ln4 | ||||||
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Title | Cryo-EM structure of human p97 in complex with Npl4/Ufd1 and polyubiquitinated Ub-Eos (FOM, Class 3) | ||||||
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Function / homology | ![]() flavin adenine dinucleotide catabolic process / positive regulation of Lys63-specific deubiquitinase activity / positive regulation of protein K63-linked deubiquitination / protein-DNA covalent cross-linking repair / VCP-NSFL1C complex / deubiquitinase activator activity / endosome to lysosome transport via multivesicular body sorting pathway / cellular response to arsenite ion / endoplasmic reticulum stress-induced pre-emptive quality control / positive regulation of oxidative phosphorylation ...flavin adenine dinucleotide catabolic process / positive regulation of Lys63-specific deubiquitinase activity / positive regulation of protein K63-linked deubiquitination / protein-DNA covalent cross-linking repair / VCP-NSFL1C complex / deubiquitinase activator activity / endosome to lysosome transport via multivesicular body sorting pathway / cellular response to arsenite ion / endoplasmic reticulum stress-induced pre-emptive quality control / positive regulation of oxidative phosphorylation / Derlin-1 retrotranslocation complex / BAT3 complex binding / mitotic spindle disassembly / ERAD pathway / VCP-NPL4-UFD1 AAA ATPase complex / NADH metabolic process / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Pan, M. / Yu, Y. / Liu, L. / Zhao, M. | ||||||
![]() | ![]() Title: Mechanistic insight into substrate processing and allosteric inhibition of human p97. Authors: Man Pan / Yuanyuan Yu / Huasong Ai / Qingyun Zheng / Yuan Xie / Lei Liu / Minglei Zhao / ![]() ![]() Abstract: p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with ...p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 Å that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 Å. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically. | ||||||
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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 | ![]() | 738.8 KB | Display | ![]() |
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PDB format | ![]() | 638.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 112.6 KB | Display | |
Data in CIF | ![]() | 159.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23448MC ![]() 7lmyC ![]() 7lmzC ![]() 7ln0C ![]() 7ln1C ![]() 7ln2C ![]() 7ln3C ![]() 7ln5C ![]() 7ln6C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 89493.852 Da / Num. of mol.: 6 / Mutation: A232E/E578Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #2: Protein/peptide | | Mass: 1890.321 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #3: Chemical | ChemComp-ADP / ![]() #4: Chemical | ChemComp-ATP / ![]() #5: Chemical | ChemComp-MG / Has ligand of interest | Y | |
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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
Component | Name: Human p97 in complex with Npl4/Ufd1 and K48-linked polyubiquitinated Ub-Eos in the presence of ATP Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19_4080: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: NONE | ||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() | ||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 723840 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||
Refine LS restraints |
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