4U95: Coupling Of Remote Alternating-access Transport Mechanisms For Protons And Substrates In The Multidrug Efflux Pump Acrb

Citation:
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 A apart. Each of these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking alpha-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.
PDB ID: 4U95Download
MMDB ID: 123909
PDB Deposition Date: 2014/8/5
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Escherichia coli K-12
Similar Structures:
Biological Unit for 4U95: pentameric; determined by author and by software (PISA)
Molecular Components in 4U95
Label Count Molecule
Proteins (5 molecules)
3
Multidrug Efflux Pump Subunit Acrb(Gene symbol: acrB)
Molecule annotation
2
Darpin
Molecule annotation
Chemicals (4 molecules)
1
3
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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