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fig 3

fig 3

Multidrugs Resistance Proteins hydrolyse ATP for the efflux of various xenobiotics. Three human MDR transporters have been found in tumor cells and transport several drugs used in chemiotherapy along with a mechanism of selectivity and inhibition poorly understood. Our team is working on bacterial homolog and on human MDRs. In absence of nucleotide, the conformation of the NBD's is open, leading to a conical shaped protein that upon reconstitution into lipid bilayer forms tubes (A). In presence of nucleotide, planar membrane and 2D crystals are formed (B). Projection map of ATP bound conformation or “NBD closed”. Centre, catalytic cycle of BmrA involving a large conformational change associated to the translocation of drugs. (Coll. S. Marco, INSERM U759, Institut Curie, A. Di Pietro, IBCP, Lyon, J.M.Jault, IBS, Grenoble).