5do7

Publication Abstract from PubMed

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 A 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.

Crystal structure of the human sterol transporter ABCG5/ABCG8.,Lee JY, Kinch LN, Borek DM, Wang J, Wang J, Urbatsch IL, Xie XS, Grishin NV, Cohen JC, Otwinowski Z, Hobbs HH, Rosenbaum DM Nature. 2016 May 4;533(7604):561-4. doi: 10.1038/nature17666. PMID:27144356^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.