Title: Cysteine Mutants of the Major Facilitator Superfamily-Type Transporter CcoA Provide Insight into Copper Import

Journal Article · · mBio (Online)
 [1];  [2];  [2];  [3];  [2];
  1. Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA, Université de Pau et des Pays de l’Adour, E2S UPPA, IPREM, UMR CNRS 5254, Pau, France
  2. Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  3. Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert Ludwigs University of Freiburg, Freiburg, Germany

Copper (Cu) is a redox-active micronutrient that is both essential and toxic. Its cellular homeostasis is critical for supporting cuproprotein maturation while avoiding excessive oxidative stress. The Cu importer CcoA is the prototype of the widespread CalT subfamily of the MFS-type transporters. Hence, understanding its molecular mechanism of function is significant. Here, we show that CcoA undergoes a thiol:disulfide oxidoreduction cycle, which is important for its Cu import activity.

Research Organization:
University of Pennsylvania, Philadelphia, PA (United States)
Sponsoring Organization:
German Research Foundation (DFG); National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division
Grant/Contract Number:
FG02-91ER20052
OSTI ID:
1808722
Journal Information:
mBio (Online), Journal Name: mBio (Online) Journal Issue: 4 Vol. 12; ISSN 2150-7511
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English

References (30)

Production of Disulfide‐Bonded Proteins in Escherichia coli journal October 2014
Heavy metal transport by the CusCFBA efflux system: Heavy Metal Transport by the CusCFBA Complex journal August 2015
Roles of the ccoGHIS gene products in the biogenesis of the cbb3-type cytochrome c oxidase journal March 2000
Molecular characterization of a copper transport protein in S. cerevisiae: An unexpected role for copper in iron transport journal January 1994
A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport journal January 1993
Biogenesis of cbb3-type cytochrome c oxidase in Rhodobacter capsulatus journal June 2012
Structural advances for the major facilitator superfamily (MFS) transporters journal March 2013
The lactose permease of Escherichia coli : overall structure, the sugar-binding site and the alternating access model for transport journal November 2003
A Mets Motif Peptide Found in Copper Transport Proteins Selectively Binds Cu(I) with Methionine-Only Coordination journal December 2005
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 journal August 1970
Alternating access mechanism in the POT family of oligopeptide transporters: Alternating access mechanism in the POT family journal June 2012
Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin journal October 2015
Understanding transport by the major facilitator superfamily (MFS): structures pave the way journal January 2016
X-ray structures of the high-affinity copper transporter Ctr1 journal March 2019
Cu Transport by the Extended Family of CcoA-like Transporters (CalT) in Proteobacteria journal February 2019
Bacterial Cu + -ATPases: models for molecular structure–function studies journal January 2016
Copper transport and regulation in Schizosaccharomyces pombe journal November 2013
Three-dimensional structure of the human copper transporter hCTR1 journal February 2009
Role of the irreplaceable residues in the LacY alternating access mechanism journal July 2012
The [2Fe-2S] Cluster E m as an Indicator of the Iron-Sulfur Subunit Position in the Ubihydroquinone Oxidation Site of the Cytochrome bc 1 Complex journal November 2001
The thioreduction component CcmG confers efficiency and the heme ligation component CcmH ensures stereo-specificity during cytochrome c maturation journal June 2017
Biochemical and Genetic Analyses of Yeast and Human High Affinity Copper Transporters Suggest a Conserved Mechanism for Copper Uptake journal April 2002
Structure and mechanism of the tripartite CusCBA heavy-metal efflux complex journal April 2012
Structure and Mechanism of the Lactose Permease of Escherichia coli journal August 2003
Major Facilitator Superfamily journal January 1998
Widespread Distribution and Functional Specificity of the Copper Importer CcoA: Distinct Cu Uptake Routes for Bacterial Cytochrome c Oxidases journal February 2018
Novel Transporter Required for Biogenesis of cbb3-Type Cytochrome c Oxidase in Rhodobacter capsulatus journal January 2012
Intracytoplasmic Copper Homeostasis Controls Cytochrome c Oxidase Production journal January 2014
Uncovering the Transmembrane Metal Binding Site of the Novel Bacterial Major Facilitator Superfamily-Type Copper Importer CcoA journal January 2016
Absence of Thiol-Disulfide Oxidoreductase DsbA Impairs cbb3-Type Cytochrome c Oxidase Biogenesis in Rhodobacter capsulatus journal December 2017