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Open data
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Basic information
Entry | Database: PDB / ID: 7kmf | ||||||
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Title | Sugar phosphate activation of the stress sensor eIF2B | ||||||
![]() | (Translation initiation factor eIF-2B subunit ...) x 5 | ||||||
![]() | TRANSLATION / Translation initiation factor eif-2b | ||||||
Function / homology | ![]() eukaryotic translation initiation factor 2B complex / Recycling of eIF2:GDP / cytoplasmic translational initiation / oligodendrocyte development / guanyl-nucleotide exchange factor complex / astrocyte development / astrocyte differentiation / regulation of translational initiation / positive regulation of translational initiation / response to glucose ...eukaryotic translation initiation factor 2B complex / Recycling of eIF2:GDP / cytoplasmic translational initiation / oligodendrocyte development / guanyl-nucleotide exchange factor complex / astrocyte development / astrocyte differentiation / regulation of translational initiation / positive regulation of translational initiation / response to glucose / ovarian follicle development / translation initiation factor binding / translational initiation / translation initiation factor activity / myelination / response to endoplasmic reticulum stress / guanyl-nucleotide exchange factor activity / central nervous system development / hippocampus development / response to peptide hormone / regulation of translation / T cell receptor signaling pathway / response to heat / positive regulation of apoptotic process / GTP binding / ATP binding / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.91 Å | ||||||
![]() | Nocek, B. / Hao, Q. / Wong, Y. / Stoll, V. / Sidrauski, C. | ||||||
![]() | ![]() Title: Sugar phosphate activation of the stress sensor eIF2B. Authors: Qi Hao / Jin-Mi Heo / Boguslaw P Nocek / Kevin G Hicks / Vincent S Stoll / Clint Remarcik / Sean Hackett / Lauren LeBon / Rinku Jain / Dan Eaton / Jared Rutter / Yao Liang Wong / Carmela Sidrauski / ![]() Abstract: The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. ...The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. The eIF2B regulatory subcomplex is evolutionarily related to sugar-metabolizing enzymes, but the biological relevance of this relationship was unknown. To identify natural ligands that might regulate eIF2B, we conduct unbiased binding- and activity-based screens followed by structural studies. We find that sugar phosphates occupy the ancestral catalytic site in the eIF2Bα subunit, promote eIF2B holoenzyme formation and enhance enzymatic activity towards eIF2. A mutant in the eIF2Bα ligand pocket that causes Vanishing White Matter disease fails to engage and is not stimulated by sugar phosphates. These data underscore the importance of allosteric metabolite modulation for proper eIF2B function. We propose that eIF2B evolved to couple nutrient status via sugar phosphate sensing with the rate of protein synthesis, one of the most energetically costly cellular processes. | ||||||
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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 | ![]() | 545.5 KB | Display | ![]() |
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PDB format | ![]() | 429.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 87.3 KB | Display | |
Data in CIF | ![]() | 132 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22924MC ![]() 7kmaC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Translation initiation factor eIF-2B subunit ... , 5 types, 10 molecules CDFEHGBIJK
#1: Protein | Mass: 41049.633 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 57640.168 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 40552.938 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: F6P / Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 80466.609 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | Mass: 50304.230 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Sugars / Non-polymers , 2 types, 20 molecules ![](data/chem/img/F6P.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/HOH.gif)
#6: Sugar | #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Tranlation initiation factor eif-2B / Type: COMPLEX / Entity ID: #1-#2, #5-#6 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 Details: Prior to grid preparation, the protein mixture was diluted with 25 mM HEPES, 100 mM KCl, 2 mM 446 MgCl2, 1 mM DTT, pH 7.5 to |
Specimen | Conc.: 0.32 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: eif2a was mixed with eif2bcde in 1.5 :1 molar ratio and incubated on ice. |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER |
Image recording | Electron dose: 44.33 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 6073 |
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Processing
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 73704 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Details: Real space refinement | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 6CAJ | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 103.98 Å2 | ||||||||||||||||||||||||
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