Alexia GODET from Aarthus university, Danemark,  has won month price for may 2025 for its article  :  Rhodamine6G and Hœchst33342 narrow BmrA conformational spectrum for a more efficient use of ATP

Alexia Gobet, 31 old, obtained her bachelor and master’s degrees in biochemistry in Claude Bernard Lyon 1 University. Then, she performed her PhD in the molecular microbiology and structural biochemistry lab in Lyon under the supervision of Vincent Chaptal and Pierre Falson. During these years, she specialized in cryo-EM and membrane proteins as she worked on the structural and functional characterization of BmrA, an exporter belonging to the ABC transporter family, to understand how they are able to resist to different drugs. She defended her PhD in july 2023 and started, a few months later, a postdoc in the molecular biology and genetics department in Aarhus University in Rasmus Kock Flygaard’s group. She woks, since then, on the structural and functional characterization of the human cardiolipin synthase, a protein from the inner mitochondrial membrane responsible for the last step of the cardiolipin synthesis. The goal is to solve its structure by cryo-EM coupled with biochemical characterization to get a better understanding of the mechanism and elucidate the reason why the absence of cardiolipin leads to diseases.

Article references

 Gobet, A., Moissonnier, L., Zarkadas, E. et al. Rhodamine6G and Hœchst33342 narrow BmrA conformational spectrum for a more efficient use of ATP. Nat Commun 16, 1745 (2025). https://doi.org/10.1038/s41467-025-56849-z

Abstract

 Multidrug ABC transporters harness the energy of ATP binding and hydrolysis to translocate substrates out of the cell and detoxify them. While this involves a well-accepted alternating access mechanism, molecular details of this interplay are still elusive. Rhodamine6G binding on a catalytic inactive mutant of the homodimeric multidrug ABC transporter BmrA triggers a cooperative binding of ATP on the two identical nucleotide-binding-sites, otherwise michaelian. Here, we investigate this asymmetric behavior via a structural- enzymology approach, solving cryoEM structures of BmrA at defined ATP ratios, highlighting the plasticity of BmrA as it undergoes the transition from inward to outward facing conformations. Analysis of continuous hetero- geneity within cryoEM data and structural dynamics, reveals that Rhodami- ne6G narrows the conformational spectrum explored by the nucleotide- binding domains. We observe the same behavior for the other drug Hœchst33342. Following on these findings, the effect of drug-binding showed an ATPase stimulation and a maximal transport activity of the wild-type pro- tein at the concentration-range where the cooperative transition occurs. Altogether, these findings provide a description of the influence of drug binding on the ATP-binding sites through a change in conformational dynamics.