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Gram-negative bacteria are capable of expelling diverse xenobioticsubstances from within the cell by use of three-componentefflux pumps in which the energy-activated inner membranetransporter is connected to the outer membrane channelprotein via the membrane fusion protein.In this work,wedescribe the crystal structure of the membrane fusion proteinMexA from the Pseudomonas aeruginosa MexAB-OprM pumpin the hexameric ring arrangement.Electron microscopy studyon the chimeric complex of MexA and the outer membrane proteinOprMrevealsthatMexAmakes a tip-to-tip interaction withOprM,which suggests a docking model for MexA and OprM.This docking model agrees well with genetic results and depictsdetailed interactions.Opening of the OprM channel is accompaniedby the simultaneous exposure of a protein structureresembling a six-bladed cogwheel,which intermeshes with thecomplementary cogwheel structure in the MexA hexamer.Taken together,we suggest an assembly and channel openingmodel for the MexAB-OprM pump.This study provides a betterunderstanding of multidrug resistance in Gram-negativebacteria.