4U96

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

4U96 の概要

• エントリーDOI: 10.2210/pdb4u96/pdb
• 分子名称: Multidrug efflux pump subunit AcrB, DARPin, DODECYL-BETA-D-MALTOSIDE, ... (4 entities in total)
• 機能のキーワード: membrane protein, transport protein, darpin, multidrug efflux protein
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Cell inner membrane ; Multi- pass membrane protein : P31224
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 384159.98

構造登録者

Pos, K.M. (登録日: 2014-08-05, 公開日: 2014-10-22, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)