6R81
Multidrug resistance transporter BmrA mutant E504A bound with ATP and Mg solved by Cryo-EM
Summary for 6R81
| Entry DOI | 10.2210/pdb6r81/pdb |
| Related | 6R72 |
| EMDB information | 4749 |
| Descriptor | Lipid A export ATP-binding/permease protein MsbA, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | membrane protein, abc transporter, multidrug resistance, transport protein |
| Biological source | Bacillus subtilis |
| Total number of polymer chains | 2 |
| Total formula weight | 132557.25 |
| Authors | Wiseman, B.,Chaptal, V.,Zampieri, V.,Magnard, S.,Hogbom, M.,Falson, P. (deposition date: 2019-03-30, release date: 2020-05-06, Last modification date: 2024-07-10) |
| Primary citation | Chaptal, V.,Zampieri, V.,Wiseman, B.,Orelle, C.,Martin, J.,Nguyen, K.A.,Gobet, A.,Di Cesare, M.,Magnard, S.,Javed, W.,Eid, J.,Kilburg, A.,Peuchmaur, M.,Marcoux, J.,Monticelli, L.,Hogbom, M.,Schoehn, G.,Jault, J.M.,Boumendjel, A.,Falson, P. Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter. Sci Adv, 8:eabg9215-eabg9215, 2022 Cited by PubMed Abstract: Multidrug ABC transporters translocate drugs across membranes by a mechanism for which the molecular features of drug release are so far unknown. Here, we resolved three ATP-Mg-bound outward-facing conformations of the (homodimeric) BmrA by x-ray crystallography and single-particle cryo-electron microscopy (EM) in detergent solution, one of them with rhodamine 6G (R6G), a substrate exported by BmrA when overexpressed in . Two R6G molecules bind to the drug-binding cavity at the level of the outer leaflet, between transmembrane (TM) helices 1-2 of one monomer and TM5'-6' of the other. They induce a rearrangement of TM1-2, highlighting a local flexibility that we confirmed by hydrogen/deuterium exchange and molecular dynamics simulations. In the absence of R6G, simulations show a fast postrelease occlusion of the cavity driven by hydrophobicity, while when present, R6G can move within the cavity, maintaining it open. PubMed: 35080979DOI: 10.1126/sciadv.abg9215 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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