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Yorodumi- EMDB-33106: Structure and mechanism of a mitochondrial AAA+ disaggregase CLPB -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33106 | |||||||||
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Title | Structure and mechanism of a mitochondrial AAA+ disaggregase CLPB | |||||||||
Map data | ||||||||||
Sample |
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Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / negative staining / Resolution: 7.5 Å | |||||||||
Authors | Wu D / Liu Y / Dai Y / Wang G / Lu G / Chen Y / Li N / Lin J / Gao N | |||||||||
Funding support | China, 1 items
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Citation | Journal: PLoS Biol / Year: 2023 Title: Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization. Authors: Damu Wu / Yan Liu / Yuhao Dai / Guopeng Wang / Guoliang Lu / Yan Chen / Ningning Li / Jinzhong Lin / Ning Gao / Abstract: The human AAA+ ATPase CLPB (SKD3) is a protein disaggregase in the mitochondrial intermembrane space (IMS) and functions to promote the solubilization of various mitochondrial proteins. Loss-of- ...The human AAA+ ATPase CLPB (SKD3) is a protein disaggregase in the mitochondrial intermembrane space (IMS) and functions to promote the solubilization of various mitochondrial proteins. Loss-of-function CLPB mutations are associated with a few human diseases with neutropenia and neurological disorders. Unlike canonical AAA+ proteins, CLPB contains a unique ankyrin repeat domain (ANK) at its N-terminus. How CLPB functions as a disaggregase and the role of its ANK domain are currently unclear. Herein, we report a comprehensive structural characterization of human CLPB in both the apo- and substrate-bound states. CLPB assembles into homo-tetradecamers in apo-state and is remodeled into homo-dodecamers upon substrate binding. Conserved pore-loops (PLs) on the ATPase domains form a spiral staircase to grip and translocate the substrate in a step-size of 2 amino acid residues. The ANK domain is not only responsible for maintaining the higher-order assembly but also essential for the disaggregase activity. Interactome analysis suggests that the ANK domain may directly interact with a variety of mitochondrial substrates. These results reveal unique properties of CLPB as a general disaggregase in mitochondria and highlight its potential as a target for the treatment of various mitochondria-related diseases. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33106.map.gz | 9.4 MB | EMDB map data format | |
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Header (meta data) | emd-33106-v30.xml emd-33106.xml | 11.8 KB 11.8 KB | Display Display | EMDB header |
Images | emd_33106.png | 49.5 KB | ||
Others | emd_33106_half_map_1.map.gz emd_33106_half_map_2.map.gz | 80.9 MB 80.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33106 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33106 | HTTPS FTP |
-Validation report
Summary document | emd_33106_validation.pdf.gz | 689.8 KB | Display | EMDB validaton report |
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Full document | emd_33106_full_validation.pdf.gz | 689.3 KB | Display | |
Data in XML | emd_33106_validation.xml.gz | 13.3 KB | Display | |
Data in CIF | emd_33106_validation.cif.gz | 15.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33106 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33106 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_33106.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.052 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33106_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33106_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Cryo-EM structure of CLPB in substrate-bound state
Entire | Name: Cryo-EM structure of CLPB in substrate-bound state |
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Components |
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-Supramolecule #1: Cryo-EM structure of CLPB in substrate-bound state
Supramolecule | Name: Cryo-EM structure of CLPB in substrate-bound state / type: complex / ID: 1 / Chimera: Yes / Parent: 0 |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | negative staining, cryo EM |
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Processing | single particle reconstruction |
Aggregation state | cell |
-Sample preparation
Buffer | pH: 6.8 |
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Staining | Type: NEGATIVE / Material: Uranyl Acetate |
Vitrification | Cryogen name: NITROGEN |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: DARK FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 7.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 53085 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |