7OZ1

Cryo-EM structure of ABCG1 E242Q mutant with ATP and cholesteryl hemisuccinate bound


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.00 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structure of the Human Cholesterol Transporter ABCG1.

Skarda, L.Kowal, J.Locher, K.P.

(2021) J Mol Biol 433: 167218-167218

  • DOI: 10.1016/j.jmb.2021.167218
  • Primary Citation of Related Structures:  
    7OZ1

  • PubMed Abstract: 
  • ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues. Despite its role in preventing lipid accumulation and the development of cardiovascular and metabolic disease, the mechanism underpinning ABCG1-mediated cholesterol transport is unknown ...

    ABCG1 is an ATP binding cassette (ABC) transporter that removes excess cholesterol from peripheral tissues. Despite its role in preventing lipid accumulation and the development of cardiovascular and metabolic disease, the mechanism underpinning ABCG1-mediated cholesterol transport is unknown. Here we report a cryo-EM structure of human ABCG1 at 4 Å resolution in an inward-open state, featuring sterol-like density in the binding cavity. Structural comparison with the multidrug transporter ABCG2 and the sterol transporter ABCG5/G8 reveals the basis of mechanistic differences and distinct substrate specificity. Benzamil and taurocholate inhibited the ATPase activity of liposome-reconstituted ABCG1, whereas the ABCG2 inhibitor Ko143 did not. Based on the structural insights into ABCG1, we propose a mechanism for ABCG1-mediated cholesterol transport.


    Organizational Affiliation

    Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zürich, Switzerland. Electronic address: locher@mol.biol.ethz.ch.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Isoform 4 of ATP-binding cassette sub-family G member 1A, B680Homo sapiensMutation(s): 1 
Gene Names: ABCG1ABC8WHT1
EC: 7.6.2
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P45844 (Homo sapiens)
Explore P45844 
Go to UniProtKB:  P45844
PHAROS:  P45844
Protein Feature View
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
PEE (Subject of Investigation/LOI)
Query on PEE

Download Ideal Coordinates CCD File 
G [auth A], N [auth B]1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
C41 H78 N O8 P
MWRBNPKJOOWZPW-NYVOMTAGSA-N
 Ligand Interaction
ATP (Subject of Investigation/LOI)
Query on ATP

Download Ideal Coordinates CCD File 
C [auth A], I [auth B]ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
 Ligand Interaction
Y01 (Subject of Investigation/LOI)
Query on Y01

Download Ideal Coordinates CCD File 
D [auth A], E [auth A], F [auth A], H [auth A], J [auth B], K [auth B], L [auth B], M [auth B]CHOLESTEROL HEMISUCCINATE
C31 H50 O4
WLNARFZDISHUGS-MIXBDBMTSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.00 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report




Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Swiss National Science FoundationSwitzerland--

Revision History  (Full details and data files)

  • Version 1.0: 2021-09-22
    Type: Initial release
  • Version 2.0: 2021-09-29
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary