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The Cus efflux system removes toxic ions via a methionine shuttle
Author(s) -
Su ChihChia,
Long Feng,
Yu Edward W.
Publication year - 2011
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.532
Subject(s) - efflux , periplasmic space , inner membrane , cell envelope , bacterial outer membrane , biochemistry , cytoplasm , biology , membrane transport protein , chemistry , biophysics , cell membrane , atp binding cassette transporter , escherichia coli , transporter , membrane , membrane protein , gene
Gram‐negative bacteria, such as Escherichia coli , frequently utilize tripartite efflux complexes in the resistance‐nodulation‐cell division (RND) family to expel diverse toxic compounds from the cell. These efflux systems span the entire cell envelope to mediate the phenomenon of bacterial multidrug resistance. The three parts of the efflux complexes are: (1) a membrane fusion protein (MFP) connecting (2) a substrate‐binding inner membrane transporter to (3) an outer membrane‐anchored channel in the periplasmic space. One such efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions. We recently determined the crystal structures of both the inner membrane transporter CusA and MFP CusB of the CusCBA tripartite efflux system from E. coli . These are the first structures of the heavy‐metal efflux (HME) subfamily of the RND efflux pumps. Here, we summarize the structural information of these two efflux proteins and present the accumulated evidence that this efflux system utilizes methionine residues to bind and export Cu(I)/Ag(I). Genetic and structural analyses suggest that the CusA pump is capable of picking up the metal ions from both the periplasm and cytoplasm. We propose a stepwise shuttle mechanism for this pump to extrude metal ions from the cell.