Structure, Mechanism and Assembly of the Tripartite CusCBA Heavy-metal Efflux Complex
Sylvia V. Do, Chih-Chia Su, Feng Long, Hsiang-Ting Lei, Jani Reddy Bolla and Edward W. Yu
from: Microbial Efflux Pumps: Current Research (Edited by: Edward W. Yu, Qijing Zhang and Melissa H. Brown). Caister Academic Press, U.K. (2013)
Abstract
Gram-negative bacteria expel various toxic chemicals via tripartite efflux pumps belonging to the resistance-nodulation-cell division (RND) superfamily. These pumps span both the inner and outer membranes of the cell. The three components of these tripartite systems are an inner membrane, substrate-binding transporter (or pump); a periplasmic membrane fusion protein (or adaptor); and an outer membrane-anchored channel. These three efflux proteins interact in the periplasmic space to form the three-part complex. One such efflux system, CusCBA, is responsible for extruding Cu(I) and Ag(I) ions, which are biocides. We previously presented the crystal structures of both the inner membrane transporter CusA and membrane fusion protein CusB of the CusCBA tripartite efflux system from Escherichia coli. We also described the co-crystal structure of the CusBA adaptor-transporter, revealing that the trimeric CusA efflux pump assembles with six CusB protein molecules to form the complex CusB6-CusA3. Recently, we reported three different conformers of the crystal structures of CusBA-Cu(I), suggesting a mechanism on how Cu(I) binding initiates a sequence of conformational transitions in the transport cycle. Herein, we summarize the structural information of these efflux proteins, and present the accumulated evidence that this efflux system utilizes conserved methionine as well as charged amino acids to bind and export Cu(I) and Ag(I) ions read more ...
