8cub

From Proteopedia

Crystal Structure of ABCG5/G8 in Complex with Cholesterol

Structural highlights

8cub is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4.05Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ABCG5_HUMAN Sitosterolemia. 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.

Publication Abstract from PubMed

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. In this study, we have determined the crystal structure of ABCG5/G8 in a cholesterol-bound state. The structure combined with amino acid sequence analysis shows that in the proximity of the sterol-binding site, a highly conserved phenylalanine array supports functional implications for ABCG cholesterol/sterol transporters. Lastly, in silico docking analysis of cholesterol and stigmasterol (a plant sterol) suggests sterol-binding selectivity on ABCG5/G8, but not ABCG1. Together, our results provide a structural basis for cholesterol binding on ABCG5/G8 and the sterol selectivity by ABCG transporters.

Structural analysis of cholesterol binding and sterol selectivity by ABCG5/G8.,Farhat D, Rezaei F, Ristovski M, Yang Y, Stancescu A, Dzimkova L, Samnani S, Couture JF, Lee JY J Mol Biol. 2022 Aug 18:167795. doi: 10.1016/j.jmb.2022.167795. PMID:35988751^[1]

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

References

↑ Farhat D, Rezaei F, Ristovski M, Yang Y, Stancescu A, Dzimkova L, Samnani S, Couture JF, Lee JY. Structural analysis of cholesterol binding and sterol selectivity by ABCG5/G8. J Mol Biol. 2022 Aug 18:167795. doi: 10.1016/j.jmb.2022.167795. PMID:35988751 doi:http://dx.doi.org/10.1016/j.jmb.2022.167795