+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-24317 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | The structure of human ABCG1 E242Q complexed with ATP | ||||||||||||
![]() | |||||||||||||
![]() |
| ||||||||||||
Function / homology | ![]() ABC-type sterol transporter activity / glycoprotein transport / cellular response to high density lipoprotein particle stimulus / intracellular cholesterol transport / toxin transmembrane transporter activity / ABC transporters in lipid homeostasis / floppase activity / positive regulation of cholesterol biosynthetic process / phosphatidylcholine floppase activity / phospholipid homeostasis ...ABC-type sterol transporter activity / glycoprotein transport / cellular response to high density lipoprotein particle stimulus / intracellular cholesterol transport / toxin transmembrane transporter activity / ABC transporters in lipid homeostasis / floppase activity / positive regulation of cholesterol biosynthetic process / phosphatidylcholine floppase activity / phospholipid homeostasis / high-density lipoprotein particle remodeling / phospholipid efflux / cholesterol transfer activity / reverse cholesterol transport / low-density lipoprotein particle remodeling / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / HDL remodeling / cholesterol efflux / regulation of cholesterol metabolic process / positive regulation of amyloid-beta formation / cholesterol binding / response to lipid / negative regulation of cholesterol storage / amyloid precursor protein catabolic process / negative regulation of macrophage derived foam cell differentiation / positive regulation of cholesterol efflux / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / cholesterol metabolic process / cholesterol homeostasis / positive regulation of protein secretion / recycling endosome / phospholipid binding / transmembrane transport / ADP binding / endosome / protein heterodimerization activity / external side of plasma membrane / Golgi membrane / endoplasmic reticulum membrane / Golgi apparatus / protein homodimerization activity / ATP hydrolysis activity / mitochondrion / ATP binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||||||||
![]() | Sun Y / Li X / Long T | ||||||||||||
Funding support | ![]()
| ||||||||||||
![]() | ![]() Title: Molecular basis of cholesterol efflux via ABCG subfamily transporters. Authors: Yingyuan Sun / Jin Wang / Tao Long / Xiaofeng Qi / Linda Donnelly / Nadia Elghobashi-Meinhardt / Leticia Esparza / Jonathan C Cohen / Xiao-Song Xie / Helen H Hobbs / Xiaochun Li / ![]() ![]() Abstract: The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular ...The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters. | ||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 10.1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 12.1 KB 12.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.8 KB | Display | ![]() |
Images | ![]() | 48.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7r8eMC ![]() 7r87C ![]() 7r88C ![]() 7r89C ![]() 7r8aC ![]() 7r8bC ![]() 7r8cC ![]() 7r8dC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 0.833 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
-Entire : ABCG1 transporter with cholesterol and ATP bound
Entire | Name: ABCG1 transporter with cholesterol and ATP bound |
---|---|
Components |
|
-Supramolecule #1: ABCG1 transporter with cholesterol and ATP bound
Supramolecule | Name: ABCG1 transporter with cholesterol and ATP bound / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Theoretical: 150 KDa |
-Macromolecule #1: Isoform 4 of ATP-binding cassette sub-family G member 1
Macromolecule | Name: Isoform 4 of ATP-binding cassette sub-family G member 1 type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO EC number: Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 74.228 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MACLMAAFSV GTAMNASSYS AEMTEPKSVC VSVDEVVSSN MEATETDLLN GHLKKVDNNL TEAQRFSSLP RRAAVNIEFR DLSYSVPEG PWWRKKGYKT LLKGISGKFN SGELVAIMGP SGAGKSTLMN ILAGYRETGM KGAVLINGLP RDLRCFRKVS C YIMQDDML ...String: MACLMAAFSV GTAMNASSYS AEMTEPKSVC VSVDEVVSSN MEATETDLLN GHLKKVDNNL TEAQRFSSLP RRAAVNIEFR DLSYSVPEG PWWRKKGYKT LLKGISGKFN SGELVAIMGP SGAGKSTLMN ILAGYRETGM KGAVLINGLP RDLRCFRKVS C YIMQDDML LPHLTVQEAM MVSAHLKLQE KDEGRREMVK EILTALGLLS CANTRTGSLS GGQRKRLAIA LELVNNPPVM FF DQPTSGL DSASCFQVVS LMKGLAQGGR SIICTIHQPS AKLFELFDQL YVLSQGQCVY RGKVCNLVPY LRDLGLNCPT YHN PADFVM EVASGEYGDQ NSRLVRAVRE GMCDSDHKRD LGGDAEVNPF LWHRPSEEDS SSMEGCHSFS ASCLTQFCIL FKRT FLSIM RDSVLTHLRI TSHIGIGLLI GLLYLGIGNE AKKVLSNSGF LFFSMLFLMF AALMPTVLTF PLEMGVFLRE HLNYW YSLK AYYLAKTMAD VPFQIMFPVA YCSIVYWMTS QPSDAVRFVL FAALGTMTSL VAQSLGLLIG AASTSLQVAT FVGPVT AIP VLLFSGFFVS FDTIPTYLQW MSYISYVRYG FEGVILSIYG LDREDLHCDI DETCHFQKSE AILRELDVEN AKLYLDF IV LGIFFISLRL IAYFVLRYKI RAER |
-Macromolecule #2: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 2 / Formula: ATP |
---|---|
Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: MG |
---|---|
Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #4: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 2 / Formula: CLR |
---|---|
Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 10 mg/mL |
---|---|
Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
Details | Added 8mM ATP, Magnesium and 0.2mg/ml cholesterol in ethanol |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 4900 / Average exposure time: 1.8 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |