Format

Send to

Choose Destination
Nature. 2016 May 26;533(7604):561-4. doi: 10.1038/nature17666. Epub 2016 May 4.

Crystal structure of the human sterol transporter ABCG5/ABCG8.

Author information

1
Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
2
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
3
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
4
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
5
Cecil &Ida Green Center for Molecular, Computational and Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
6
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.

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.

PMID:
27144356
PMCID:
PMC4964963
DOI:
10.1038/nature17666
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Supplementary concept, Grant support

Publication types

MeSH terms

Substances

Supplementary concept

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center