Structural highlights
Disease
[ABCG5_HUMAN] Sitosterolemia. The disease is caused by mutations affecting the gene represented in this entry. [ABCG8_HUMAN] Sitosterolemia. Disease susceptibility may be associated with variations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[ABCG5_HUMAN] Transporter that appears to play an indispensable role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile. [ABCG8_HUMAN] Transporter that appears to play an indispensable role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile.
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.
References
- ↑ Lee JY, Kinch LN, Borek DM, Wang J, Wang J, Urbatsch IL, Xie XS, Grishin NV, Cohen JC, Otwinowski Z, Hobbs HH, Rosenbaum DM. Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature. 2016 May 4;533(7604):561-4. doi: 10.1038/nature17666. PMID:27144356 doi:http://dx.doi.org/10.1038/nature17666
