, 23:1 | Cite as

EfeO-cupredoxins: major new members of the cupredoxin superfamily with roles in bacterial iron transport

  • Mohan B. Rajasekaran
  • Sanjay Nilapwar
  • Simon C. AndrewsEmail author
  • Kimberly A. Watson


The EfeUOB system of Escherichia coli is a tripartite, low pH, ferrous iron transporter. It resembles the high-affinity iron transporter (Ftr1p-Fet3p) of yeast in that EfeU is homologous to Ftr1p, an integral-membrane iron-permease. However, EfeUOB lacks an equivalent of the Fet3p component—the multicopper oxidase with three cupredoxin-like domains. EfeO and EfeB are periplasmic but their precise roles are unclear. EfeO consists primarily of a C-terminal peptidase-M75 domain with a conserved ‘HxxE’ motif potentially involved in metal binding. The smaller N-terminal domain (EfeO-N) is predicted to be cupredoxin (Cup) like, suggesting a previously unrecognised similarity between EfeO and Fet3p. Our structural modelling of the E. coli EfeO Cup domain identifies two potential metal-binding sites. Site I is predicted to bind Cu2+ using three conserved residues (C41 and 103, and E66) and M101. Of these, only one (C103) is conserved in classical cupredoxins where it also acts as a Cu ligand. Site II most probably binds Fe3+ and consists of four well conserved surface Glu residues. Phylogenetic analysis indicates that the EfeO-Cup domains form a novel Cup family, designated the ‘EfeO-Cup’ family. Structural modelling of two other representative EfeO-Cup domains indicates that different subfamilies employ distinct ligand sets at their proposed metal-binding sites. The ~100 efeO homologues in the bacterial sequence databases are all associated with various iron-transport related genes indicating a common role for EfeO-Cup proteins in iron transport, supporting a new copper-iron connection in biology.


Iron transport Homology modelling Cupredoxin Electron transfer GRID prediction Metal binding site DUF451 Peptidase-M75 



We thank Peter Goodford and Jim Dunwell for helpful discussions in the preparation of the manuscript. We also thank Liam McGuffin for the helpful discussions related with the evaluation of structural models. Authors thank FELIX trust, Biotechnology and Biological Sciences Research (BBSRC) and Lister Institute of Preventive Medicine for providing funding for this study. We thank Sue Mitchell and Nick Spencer (Structural Biology Unit, The Biocentre) for technical support.

Supplementary material

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(DOC 2472 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Mohan B. Rajasekaran
    • 1
    • 2
  • Sanjay Nilapwar
    • 3
  • Simon C. Andrews
    • 1
    Email author
  • Kimberly A. Watson
    • 1
    • 2
  1. 1.School of Biological SciencesUniversity of ReadingReadingUK
  2. 2.Structural Biology Unit at The BiocentreUniversity of ReadingReadingUK
  3. 3.Manchester Interdisciplinary BiocentreUniversity of ManchesterManchesterUK

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