Structural Analysis of Cholesterol Binding and Sterol Selectivity by ABCG5/G8.
J Mol Biol
; 434(20): 167795, 2022 10 30.
Article
in En
| MEDLINE
| ID: mdl-35988751
ABSTRACT
The ATP-binding cassette (ABC) sterol transporters are responsible for maintaining cholesterol homeostasis in mammals by participating in reverse cholesterol transport (RCT) or transintestinal cholesterol efflux (TICE). The heterodimeric ABCG5/G8 carries out selective sterol excretion, preventing the abnormal accumulation of plant sterols in human bodies, while homodimeric ABCG1 contributes to the biogenesis and metabolism of high-density lipoproteins. A sterol-binding site on ABCG5/G8 was proposed at the interface of the transmembrane domain and the core of lipid bilayers. In this study, we have determined the crystal structure of ABCG5/G8 in a cholesterol-bound state. The structure combined with amino acid sequence analysis shows that in the proximity of the sterol-binding site, a highly conserved phenylalanine array supports functional implications for ABCG cholesterol/sterol transporters. Lastly, in silico docking analysis of cholesterol and stigmasterol (a plant sterol) suggests sterol-binding selectivity on ABCG5/G8, but not ABCG1. Together, our results provide a structural basis for cholesterol binding on ABCG5/G8 and the sterol selectivity by ABCG transporters.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cholesterol
/
ATP Binding Cassette Transporter, Subfamily G, Member 5
/
ATP Binding Cassette Transporter, Subfamily G, Member 8
Limits:
Humans
Language:
En
Journal:
J Mol Biol
Year:
2022
Document type:
Article