8GMG
CryoEM structure of P-Glycoprotein in Apo state
Summary for 8GMG
| Entry DOI | 10.2210/pdb8gmg/pdb |
| Related | 8GMJ |
| EMDB information | 40226 40227 |
| Descriptor | ATP-dependent translocase ABCB1 (1 entity in total) |
| Functional Keywords | multidrug resistance, abc transporter, membrane protein, transporter, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 141644.78 |
| Authors | Culbertson, A.,Liao, M. (deposition date: 2023-03-25, release date: 2025-04-23, Last modification date: 2025-05-21) |
| Primary citation | Culbertson, A.T.,Liao, M. Cryo-EM of human P-glycoprotein reveals an intermediate occluded conformation during active drug transport. Nat Commun, 16:3619-3619, 2025 Cited by PubMed Abstract: P-glycoprotein (Pgp) is an important human multidrug transporter that contributes to pharmacokinetics and multidrug resistance. Despite decades of study, the conformation transition cycle of Pgp undergoing active drug transport is not defined, thus the precise relevance of all available Pgp structures to uninterrupted multidrug transport remains unclear. Here, we use cryo-EM of membrane-embedded human Pgp under continuous turnover conditions to analyze the conformational ensembles of Pgp transporting distinct substrates. These results delineate multiple conformations including inward-facing and closed conformations, highlighting the occluded conformation as a critical intermediate state between transporter closure and substrate release. A combination of structural, functional, and computational studies reveals the transmembrane helices 4 and 10 undergoing drastic rearrangement to coordinate substrate binding, occlusion, and release, and identifies a peripheral site involved in substrate capture and Pgp inhibition. Together, our results provide a set of snapshots of Pgp undergoing continuous drug transport, unveiling the intricate interplay between transporter dynamics and drug movement, and shed light on the mechanism of polyspecificity. PubMed: 40240353DOI: 10.1038/s41467-025-58561-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.3 Å) |
Structure validation
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