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- EMDB-22443: Cryo-EM structure of ABCG5/G8 in complex with Fab 2E10 and 11F4 -
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Open data
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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 | |||||||||
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Function / homology | ![]() negative regulation of intestinal phytosterol absorption / negative regulation of intestinal cholesterol absorption / Defective ABCG8 causes GBD4 and sitosterolemia / Defective ABCG5 causes sitosterolemia / sterol transport / ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Huang CS / Yu X / Min X / Wang Z / Zhang H | |||||||||
![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 166.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.5 KB 18.5 KB | Display Display | ![]() |
Images | ![]() | 69.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7jr7MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
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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 | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
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 |
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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 |