6VXF
Structure of apo-closed ABCG2
Summary for 6VXF
| Entry DOI | 10.2210/pdb6vxf/pdb |
| EMDB information | 21436 21437 21438 21439 21440 21441 |
| Descriptor | Broad substrate specificity ATP-binding cassette transporter ABCG2 (1 entity in total) |
| Functional Keywords | abcg2, bcrp, nanodisc, abc transporter, translocase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 144771.70 |
| Authors | Orlando, B.J.,Maofu, L. (deposition date: 2020-02-21, release date: 2020-05-13, Last modification date: 2025-06-04) |
| Primary citation | Orlando, B.J.,Liao, M. ABCG2 transports anticancer drugs via a closed-to-open switch. Nat Commun, 11:2264-2264, 2020 Cited by PubMed Abstract: ABCG2 is an ABC transporter that extrudes a variety of compounds from cells, and presents an obstacle in treating chemotherapy-resistant cancers. Despite recent structural insights, no anticancer drug bound to ABCG2 has been resolved, and the mechanisms of multidrug transport remain obscure. Such a gap of knowledge limits the development of novel compounds that block or evade this critical molecular pump. Here we present single-particle cryo-EM studies of ABCG2 in the apo state, and bound to the three structurally distinct chemotherapeutics. Without the binding of conformation-selective antibody fragments or inhibitors, the resting ABCG2 adopts a closed conformation. Our cryo-EM, biochemical, and functional analyses reveal the binding mode of three chemotherapeutic compounds, demonstrate how these molecules open the closed conformation of the transporter, and establish that imatinib is particularly effective in stabilizing the inward facing conformation of ABCG2. Together these studies reveal the previously unrecognized conformational cycle of ABCG2. PubMed: 32385283DOI: 10.1038/s41467-020-16155-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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