ABCG5/G8 Crystallization in a Lipidic Bicelle Environment for X-Ray Crystallography.

ATP-binding cassette (ABC) transporters constitute lipid-embedded membrane proteins. Extracting these membrane proteins from the lipid bilayer to an aqueous environment is typically achieved by employing detergents. These detergents disintegrate the lipid bilayer and solubilize the proteins.

Snapshots of ABCG1 and ABCG5/G8: A Sterol's Journey to Cross the Cellular Membranes.

The subfamily-G ATP-binding cassette (ABCG) transporters play important roles in regulating cholesterol homeostasis. Recent progress in the structural data of ABCG1 and ABCG5/G8 disclose putative sterol binding sites that suggest the possible cholesterol translocation pathway. ABCG1 and ABCG5/G8 share high similarity in the overall molecular architecture, and both transporters appear to use several unique structural motifs to facilitate cholesterol transport along this pathway, including the phenylalanine highway and the hydrophobic valve.

Data on structural analysis of cholesterol binding and sterol selectivity by ABCG5/G8.

ATP-Binding cassette subfamily G (ABCG) sterol transporters maintain whole body endogenous and exogenous sterol homeostasis. A substantial portion of exogenous sterols are undigestible phytosterols (plant sterols), which can introduce complications when accumulated. ABCG5/G8 is the main protein functioning to remove ingested plant sterols providing protection from their toxic effects, although, the structural features behind substrate binding in ABCG5/G8 remain poorly resolved.

Structural Analysis of Cholesterol Binding and Sterol Selectivity by ABCG5/G8.

The ATP-binding cassette (ABC) sterol transporters are responsible for maintaining cholesterol homeostasis in mammals by participating in reverse cholesterol transport (RCT) or transintestinal cholesterol efflux (TICE). The heterodimeric ABCG5/G8 carries out selective sterol excretion, preventing the abnormal accumulation of plant sterols in human bodies, while homodimeric ABCG1 contributes to the biogenesis and metabolism of high-density lipoproteins. A sterol-binding site on ABCG5/G8 was proposed at the interface of the transmembrane domain and the core of lipid bilayers.

Lipid Transporters Beam Signals from Cell Membranes.

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.