4U8Y
Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB
Summary for 4U8Y
| Entry DOI | 10.2210/pdb4u8y/pdb |
| Related | 4U8V |
| 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 | 383340.98 |
| 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.,Brandstatter, 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 Cited by 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: 25248080DOI: 10.7554/eLife.03145 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.099 Å) |
Structure validation
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