Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB.

ABSTRACT: Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug antiporter AcrB, the active component of the major efflux system AcrAB-TolC in Escherichia coli, and one most complex and intriguing membrane transporters known to date. Analysis of wildtype AcrB and four functionally-inactive variants reveals an unprecedented mechanism that involves two remote alternating-access conformational cycles within each protomer, namely one for protons in the transmembrane region and another for drugs in the periplasmic domain, 50 Å apart. Each of the

SUBMITTER: Eicher T 

PROVIDER: S-EPMC4359379 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature