title: The Cus efflux system removes toxic ions via a methionine shuttle.
abstract: 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.
authors.affiliation: Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Su
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.forename: Edward W
authors.initials: EW
authors.lastname: Yu
mesh_terms: D003300:Copper / Q000378:metabolism / Q000633:toxicity; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000502:physiology*; D016623:Ion Pumps / Q000737:chemistry / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000502:physiology*; D019216:Metals, Heavy / Q000378:metabolism* / Q000633:toxicity; D008715:Methionine / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012834:Silver / Q000378:metabolism / Q000633:toxicity
chemical_list: C552999:CusA protein, E coli; C556452:CusB protein, E coli; C096350:CusC protein, E coli; D029968:Escherichia coli Proteins; D016623:Ion Pumps; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D019216:Metals, Heavy; D012834:Silver; D003300:Copper; D008715:Methionine