Crystal structure of the human sterol transporter ABCG5/ABCG8.
Nature
; 533(7604): 561-4, 2016 05 26.
Article
in En
| MEDLINE
| ID: mdl-27144356
ABSTRACT
ATP binding cassette (ABC) transporters play critical roles in maintaining sterol balance in higher eukaryotes. The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines. Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis. Here we use crystallization in lipid bilayers to determine the X-ray structure of human G5G8 in a nucleotide-free state at 3.9 Å resolution, generating the first atomic model of an ABC sterol transporter. The structure reveals a new transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide-binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. The G5G8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolaemia.
Full text:
1
Database:
MEDLINE
Main subject:
Sterols
/
ATP-Binding Cassette Transporters
/
Lipoproteins
Limits:
Humans
Language:
En
Journal:
Nature
Year:
2016
Type:
Article
Affiliation country:
United States