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-Structure paper
タイトル | Molecular basis of cholesterol efflux via ABCG subfamily transporters. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 118, Issue 34, Year 2021 |
掲載日 | 2021年8月24日 |
著者 | Yingyuan Sun / Jin Wang / Tao Long / Xiaofeng Qi / Linda Donnelly / Nadia Elghobashi-Meinhardt / Leticia Esparza / Jonathan C Cohen / Xiao-Song Xie / Helen H Hobbs / Xiaochun Li / |
PubMed 要旨 | The 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 ...The 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. |
リンク | Proc Natl Acad Sci U S A / PubMed:34404721 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.6 - 3.7 Å |
構造データ | EMDB-24310, PDB-7r87: EMDB-24311, PDB-7r88: EMDB-24312, PDB-7r89: EMDB-24313, PDB-7r8a: EMDB-24314, PDB-7r8b: EMDB-24315, PDB-7r8c: EMDB-24316, PDB-7r8d: EMDB-24317, PDB-7r8e: |
化合物 | ChemComp-ERG: ChemComp-CLR: ChemComp-ATP: ChemComp-MG: |
由来 |
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キーワード | LIPID TRANSPORT/IMMUNE SYSTEM / sterol / lipids / ABC transporter / LIPID TRANSPORT / LIPID TRANSPORT-IMMUNE SYSTEM complex |