4C48

Crystal structure of AcrB-AcrZ complex

4C48 の概要

• エントリーDOI: 10.2210/pdb4c48/pdb
• 分子名称: ACRIFLAVINE RESISTANCE PROTEIN B, DARPIN, UNCHARACTERIZED MEMBRANE PROTEIN YBHT, ... (6 entities in total)
• 機能のキーワード: transport protein, drug efflux, transmembrane protein
• 由来する生物種: ESCHERICHIA COLI K-12; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 141665.12

構造登録者

Du, D.,James, N.,Klimont, E.,Luisi, B.F. (登録日: 2013-09-02, 公開日: 2014-04-30, 最終更新日: 2023-12-20)

主引用文献

Du, D.,Wang, Z.,James, N.R.,Voss, J.E.,Klimont, E.,Ohene-Agyei, T.,Venter, H.,Chiu, W.,Luisi, B.F.
Structure of the AcrAB-TolC multidrug efflux pump.
Nature, 509:512-515, 2014

PubMed Abstract: The capacity of numerous bacterial species to tolerate antibiotics and other toxic compounds arises in part from the activity of energy-dependent transporters. In Gram-negative bacteria, many of these transporters form multicomponent 'pumps' that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component. A model system for such a pump is the acridine resistance complex of Escherichia coli. This pump assembly comprises the outer-membrane channel TolC, the secondary transporter AcrB located in the inner membrane, and the periplasmic AcrA, which bridges these two integral membrane proteins. The AcrAB-TolC efflux pump is able to transport vectorially a diverse array of compounds with little chemical similarity, thus conferring resistance to a broad spectrum of antibiotics. Homologous complexes are found in many Gram-negative species, including in animal and plant pathogens. Crystal structures are available for the individual components of the pump and have provided insights into substrate recognition, energy coupling and the transduction of conformational changes associated with the transport process. However, how the subunits are organized in the pump, their stoichiometry and the details of their interactions are not known. Here we present the pseudo-atomic structure of a complete multidrug efflux pump in complex with a modulatory protein partner from E. coli. The model defines the quaternary organization of the pump, identifies key domain interactions, and suggests a cooperative process for channel assembly and opening. These findings illuminate the basis for drug resistance in numerous pathogenic bacterial species.

PubMed: 24747401
DOI: 10.1038/nature13205

実験手法

X-RAY DIFFRACTION (3.3 Å)