Conformational changes in a multidrug resistance ABC transporter DrrAB: Fluorescence-based approaches to study substrate binding.
Conformational changes in a multidrug resistance ABC transporter DrrAB: Fluorescence-based approaches to study substrate binding.
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DOI：
10.1016/j.abb.2018.09.017
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发表时间：
2018-11-15
影响因子：
3.9
通讯作者：
Kaur P
中科院分区：
文献类型：
--
作者：
Rahman SJ;Kaur P
Bacterial multidrug transporter DrrAB exhibits overlapping substrate specificity with mammalian Pglycoprotein. DrrA hydrolyzes ATP, and the energy is transduced to carrier DrrB resulting in export of drugs. Previous studies suggested that DrrB contains a large and flexible drug-binding pocket made of aromatic residues contributed by several transmembrane helices with different drugs binding to both specific and shared residues in this pocket. However, direct binding of drugs to DrrAB or the mechanism of substrate-induced conformational changes between DrrA and DrrB has so far not been investigated. We used two fluorescence-based approaches to determine substrate binding to purified DrrAB. Our analysis shows that DrrB binds drugs with variable affinities and contains multiple drug binding sites. This work also provides evidence for two asymmetric nucleotide binding sites in DrrA with strikingly different binding affinities. Using targeted fluorescence labeling, we provide clear evidence of long-range conformational changes occurring between DrrA and DrrB. It is proposed that the transduction pathway from the nucleotide-binding DrrA subunit to the substrate binding DrrB subunit includes Q-loop and CREEM motifs in DrrA and EAA-like motif in DrrB. This study lays a solid groundwork for examining roles of various conserved regions of DrrA and DrrB in transduction of conformational changes.
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影响因子：
8
作者：
Li, Jingzhi;Jaimes, Kimberly F.;Aller, Stephen G.
通讯作者：
Aller, Stephen G.
影响因子：
2.9
作者：
Kaur, P;Rao, DK;Gandlur, SM
通讯作者：
Gandlur, SM
DOI：
10.1126/science.1168750
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aller SG;Yu J;Ward A;Weng Y;Chittaboina S;Zhuo R;Harrell PM;Trinh YT;Zhang Q;Urbatsch IL;Chang G
通讯作者：
Chang G
影响因子：
4.1
作者：
Buche, A;Mendez, C;Salas, JA
通讯作者：
Salas, JA
影响因子：
4.8
作者：
Eckford, Paul D. W.;Sharom, Frances J.
通讯作者：
Sharom, Frances J.