4U95

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

Summary for 4U95

• Entry DOI: 10.2210/pdb4u95/pdb
• Descriptor: Multidrug efflux pump subunit AcrB, DARPin, DODECYL-BETA-D-MALTOSIDE, ... (5 entities in total)
• Functional Keywords: membrane protein, transport protein, darpin, multidrug efflux protein
• Biological source: Escherichia coli; More
• Cellular location: Cell inner membrane ; Multi- pass membrane protein : P31224
• Total number of polymer chains: 5
• Total formula weight: 382659.04

Authors

Pos, K.M. (deposition date: 2014-08-05, release date: 2014-10-15, Last modification date: 2023-12-20)

Primary citation

Eicher, T.,Seeger, M.A.,Anselmi, C.,Zhou, W.,Brandstaetter, L.,Verrey, F.,Diederichs, K.,Faraldo-Gomez, J.D.,Pos, K.M.
Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB
eLife, 3:e03145-, 2014

PubMed 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 these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking α-helices that project from the membrane. Moreover, we rationalize how the cross-talk among protomers across the trimerization interface might lead to a more kinetically efficient efflux system.

PubMed: 25248080
DOI: 10.7554/eLife.03145

Experimental method

X-RAY DIFFRACTION (2 Å)