Abstract
Abstract While mechanosensitive ion channels’ gating has been well documented, the effect of membrane mechanics, in particular membrane curvature, on the function of transporters remains elusive. Since conical shape transmembrane proteins locally deform membranes, conversely membrane bending could impact their conformations and their function. We tested this hypothesis using BmrA, a bacterial ABC exporter that exhibits large conformational changes upon ATP hydrolysis, switching between open and closed states with opposite V-shapes. After reconstitution in liposomes of different curvatures, we showed that BmrA ATPase activity decreases by 2.9-fold when their diameter decreases from 125 to 29 nm. Moreover, using single-molecule FRET, we observed that the fraction of closed conformations is significantly reduced in highly curved vesicles when adding ATP or non-hydrolysable AMP-PNP. Our results are well explained by a theoretical 2-states model including the effect of membrane mechanics on protein shape transition. Our work reveals that the functional cycle of conical transporters is curvature sensitive, to an extent depending on protein geometry. Teaser High membrane curvature strongly impacts the functional cycle of transporters.