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Yorodumi- EMDB-22443: Cryo-EM structure of ABCG5/G8 in complex with Fab 2E10 and 11F4 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22443 | |||||||||
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Title | Cryo-EM structure of ABCG5/G8 in complex with Fab 2E10 and 11F4 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information negative regulation of intestinal phytosterol absorption / negative regulation of intestinal cholesterol absorption / Defective ABCG8 causes GBD4 and sitosterolemia / Defective ABCG5 causes sitosterolemia / sterol transport / ABC transporters in lipid homeostasis / intestinal cholesterol absorption / cholesterol transfer activity / phospholipid transport / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate ...negative regulation of intestinal phytosterol absorption / negative regulation of intestinal cholesterol absorption / Defective ABCG8 causes GBD4 and sitosterolemia / Defective ABCG5 causes sitosterolemia / sterol transport / ABC transporters in lipid homeostasis / intestinal cholesterol absorption / cholesterol transfer activity / phospholipid transport / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / triglyceride homeostasis / response to muscle activity / bile acid signaling pathway / cholesterol efflux / response to ionizing radiation / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / ATP-binding cassette (ABC) transporter complex / response to nutrient / cholesterol homeostasis / transmembrane transport / receptor complex / response to xenobiotic stimulus / apical plasma membrane / protein heterodimerization activity / ATP hydrolysis activity / ATP binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Huang CS / Yu X / Min X / Wang Z / Zhang H | |||||||||
Citation | Journal: Commun Biol / Year: 2021 Title: Cryo-EM structure of ABCG5/G8 in complex with modulating antibodies. Authors: Hanzhi Zhang / Ching-Shin Huang / Xinchao Yu / Jonas Lee / Amit Vaish / Qing Chen / Mingyue Zhou / Zhulun Wang / Xiaoshan Min / Abstract: The heterodimer of ATP-binding cassette transporter ABCG5 and ABCG8 mediates the excretion of sterols from liver and intestine, playing a critical role in cholesterol homeostasis. Here, we present ...The heterodimer of ATP-binding cassette transporter ABCG5 and ABCG8 mediates the excretion of sterols from liver and intestine, playing a critical role in cholesterol homeostasis. Here, we present the cryo-EM structure of ABCG5/G8 in complex with the Fab fragments from two monoclonal antibodies at 3.3Å resolution. The high-resolution structure reveals a unique dimer interface between the nucleotide-binding domains (NBD) of opposing transporters, consisting of an ordered network of salt bridges between the conserved NPXDFXXD motif and serving as a pivot point that may be important for the transport cycle. While mAb 11F4 increases the ATPase activity potentially by stabilization of the NBD dimer formation, mAb 2E10 inhibits ATP hydrolysis, likely by restricting the relative movement between the RecA and helical domain of ABCG8 NBD. Our study not only provides insights into the structural elements important for the transport cycle but also reveals novel epitopes for potential therapeutic interventions. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22443.map.gz | 166.9 MB | EMDB map data format | |
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Header (meta data) | emd-22443-v30.xml emd-22443.xml | 18.5 KB 18.5 KB | Display Display | EMDB header |
Images | emd_22443.png | 69.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22443 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22443 | HTTPS FTP |
-Related structure data
Related structure data | 7jr7MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_22443.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.0588 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : ABCG5/G8 in complex with Fab 2E10 and 11F4
+Supramolecule #1: ABCG5/G8 in complex with Fab 2E10 and 11F4
+Supramolecule #2: ABCG5/G8
+Supramolecule #3: Fab 11F4
+Supramolecule #4: Fab 2E10
+Macromolecule #1: ATP-binding cassette sub-family G member 5
+Macromolecule #2: ATP-binding cassette sub-family G member 8
+Macromolecule #3: Fab 11F4 heavy chain
+Macromolecule #4: Fab 11F4 light chain
+Macromolecule #5: Fab 2E10 heavy chain
+Macromolecule #6: Fab 2E10 light chain
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 47.5 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Software - Name: Gctf (ver. 1.06) |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.0) |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 492931 |