5NJ3
Structure of an ABC transporter: complete structure
Summary for 5NJ3
| Entry DOI | 10.2210/pdb5nj3/pdb |
| EMDB information | 3654 |
| Descriptor | ATP-binding cassette sub-family G member 2, 5D3-Fab heavy chain, 5D3-Fab light chain, ... (4 entities in total) |
| Functional Keywords | abc transporter, transport protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 242515.58 |
| Authors | Taylor, N.M.I.,Manolaridis, I.,Jackson, S.M.,Kowal, J.,Stahlberg, H.,Locher, K.P. (deposition date: 2017-03-28, release date: 2017-06-07, Last modification date: 2024-11-13) |
| Primary citation | Taylor, N.M.I.,Manolaridis, I.,Jackson, S.M.,Kowal, J.,Stahlberg, H.,Locher, K.P. Structure of the human multidrug transporter ABCG2. Nature, 546:504-509, 2017 Cited by PubMed Abstract: ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of human ABCG2 determined by cryo-electron microscopy, providing the first high-resolution insight into a human multidrug transporter. We visualize ABCG2 in complex with two antigen-binding fragments of the human-specific, inhibitory antibody 5D3 that recognizes extracellular loops of the transporter. We observe two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between the transmembrane domains. Combined with functional in vitro analyses, our results suggest a multidrug recognition and transport mechanism of ABCG2, rationalize disease-causing single nucleotide polymorphisms and the allosteric inhibition by the 5D3 antibody, and provide the structural basis of cholesterol recognition by other G-subfamily ABC transporters. PubMed: 28554189DOI: 10.1038/nature22345 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.78 Å) |
Structure validation
Download full validation report
