9CTG
SapNP Reconstituted Human ABCB1 bound to ATP gammaS
Summary for 9CTG
| Entry DOI | 10.2210/pdb9ctg/pdb |
| Related | 9CR8 9CTC 9CTF |
| EMDB information | 45854 45903 45904 45906 |
| Descriptor | ATP-dependent translocase ABCB1, UNKNOWN BRANCHED FRAGMENT OF PHOSPHOLIPID, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | abcb1, p-gp, atpgammas bound, nanoparticle, saposin a, non-hydrolysable nucleotide, membrane protein, pgp, mdr1, translocase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 147050.16 |
| Authors | |
| Primary citation | Kurre, D.,Dang, P.X.,Le, L.T.M.,Gadkari, V.V.,Alam, A. Structural insights into binding-site access and ligand recognition by human ABCB1. Embo J., 2025 Cited by PubMed Abstract: ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.4-3.9 Å resolution, in the absence of stabilizing antibodies or mutations. The substrate-binding site is located within one half of the molecule and, in the apo state, is obstructed by the transmembrane helix (TM) 4. Substrate and inhibitor binding are distinguished by major TM rearrangements and their ligand binding chemistry, with TM4 playing a central role in all conformational transitions. Furthermore, our data identify secondary structure-breaking residues that impart localized TM flexibility and asymmetry between the two transmembrane domains. The resulting structural changes and lipid interactions that are induced by substrate and inhibitor binding can predict substrate-binding profiles and may direct ABCB1 inhibitor design. PubMed: 39806099DOI: 10.1038/s44318-025-00361-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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