4u96

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

spinqualitylabelsall models 4u96, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4u96 is a 5 chain structure with sequence from Escherichia coli K-12 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: LMT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACRB_ECOLI AcrAB is a drug efflux protein with a broad substrate specificity. Publication Abstract from PubMed 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. Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB.,Eicher T, Seeger MA, Anselmi C, Zhou W, Brandstatter L, Verrey F, Diederichs K, Faraldo-Gomez JD, Pos KM Elife. 2014 Sep 19;3. doi: 10.7554/eLife.03145. PMID:25248080 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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