6R72

Crystal structure of BmrA-E504A in an outward-facing conformation

Summary for 6R72

• Entry DOI: 10.2210/pdb6r72/pdb
• Descriptor: Multidrug exporter ATP-binding cassette, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: abc transporter bmra multi-drug transporter, transport protein
• Biological source: Bacillus subtilis
• Total number of polymer chains: 4
• Total formula weight: 265114.51

Authors

Chaptal, V.,Zampieri, V.,Kilburg, A.,Magnard, S.,Falson, P. (deposition date: 2019-03-28, release date: 2020-05-06, Last modification date: 2024-01-24)

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

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: 35080979
DOI: 10.1126/sciadv.abg9215

Experimental method

X-RAY DIFFRACTION (3.95 Å)