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

Biometals. 2010 Feb;23(1):1-17. doi: 10.1007/s10534-009-9262-z. Epub 2009 Aug 23.

Abstract

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 Cu(2+) 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 Fe(3+) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Azurin / metabolism*
  • Biological Transport
  • Cation Transport Proteins / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Iron / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Alignment

Substances

  • Cation Transport Proteins
  • Escherichia coli Proteins
  • cupredoxin
  • efeU' protein, E coli
  • Azurin
  • Iron