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Fig.3
Les protéines de multi-résistance aux molécules hydrophobes hydrolysent l'ATP pour l'efflux de divers xénobiotiques. Trois transporteurs MDR humains ont été trouvés dans des cellules tumorales et transportent plusieurs médicaments utilisés en chimiothérapie avec un mécanisme de sélectivité et d'inhibition encore mal compris. Notre équipe travaille sur les homologues bactériens et les MDR humains. En l'absence de nucléotide, la conformation des NBD est ouverte, ce qui conduit à une protéine de forme conique, qui après reconstitution dans une bicouche lipidique forme des structures tubulaires (A). En présence de nucléotide, une membrane plane et des cristaux 2D se forment (B). Carte de projection en conformation après fixation d'ATP ou «NBD fermé». Au centre, cycle catalytique de BmrA impliquant un important changement conformationel associé à la translocation de substrats. (Coll. S. Marco, INSERM U759, Institut Curie, A. Di Pietro, IBCP, Lyon, J.M. Jault, IBS, Grenoble).