7r87 | pdb_00007r87
The structure of human ABCG5-WT/ABCG8-I419E
Structural highlights
DiseaseABCG5_HUMAN Sitosterolemia. The disease is caused by mutations affecting the gene represented in this entry. FunctionABCG5_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 PubMedThe ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters. Molecular basis of cholesterol efflux via ABCG subfamily transporters.,Sun Y, Wang J, Long T, Qi X, Donnelly L, Elghobashi-Meinhardt N, Esparza L, Cohen JC, Xie XS, Hobbs HH, Li X Proc Natl Acad Sci U S A. 2021 Aug 24;118(34). pii: 2110483118. doi:, 10.1073/pnas.2110483118. PMID:34404721[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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