Structure of the Dietzia Mrp complex reveals molecular mechanism of this giant bacterial sodium proton pump

Significance Multiple resistance and pH adaptation (Mrp) complexes are the most sophisticated known cation/proton exchangers and are essential for the survival of a vast variety of alkaliphilic and/or halophilic microorganisms. Moreover, this family of antiporters represents the ancestor of cation pumps in nearly all known redox-driven transporter complexes, including the complex I of the respiratory chain. For the Mrp complex, an experimental structure is lacking. We now report the structure of Mrp complex at 3.0-Å resolution solved using the single-particle cryo-EM method. The structure-inspired functional study of Mrp provides detailed information for further biophysical and biochemical investigation of the intriguingly pumping mechanism and physiological functions of this complex, as well as for exploring its potential as a therapeutic drug target.