Characterization of a Dipartite Iron Uptake System from Uropathogenic Escherichia coli Strain

Authors

Doreen Koch, Martin-Luther-University Halle-Wittenberg
Anson C. K. Chan, University of British Columbia, Vancouver
Michael E.P. Murphy, University of British Columbia, Vancouver
Hauke Lilie, Martin-Luther-University Halle-Wittenberg
Gregor Grass, Bundeswehr Institute of MicrobiologyFollow
Dietrich H. Nies, Martin-Luther-University Halle-Wittenberg

Date of this Version

2011

Citation

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 286, NO. 28, pp. 25317–25330, July 15, 2011

Comments

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Abstract

In the uropathogenic Escherichia coli strain F11, in silico genome analysis revealed the dicistronic iron uptake operon fetMP, which is under iron-regulated control mediated by the Fur regulator. The expression of fetMP in a mutant strain lacking known iron uptake systems improved growth under iron depletion and increased cellular iron accumulation. FetM is a member of the iron/lead transporter superfamily and is essential for iron uptake by the Fet system. FetP is a periplasmic protein that enhanced iron uptake by FetM. Recombinant FetP bound Cu(II) and the iron analog Mn(II) at distinct sites. The crystal structure of the FetP dimer reveals a copper site in each FetP subunit that adopts two conformations: CuA with a tetrahedral geometry composed of His⁴⁴, Met⁹⁰, His⁹⁷, and His¹²⁷, and CuB, a second degenerate octahedral geometry with the addition of Glu⁴⁶. The copper ions of each site occupy distinct positions and are separated by 1.3A . Nearby, a putative additional Cu(I) binding site is proposed as an electron source that may function with CuA/CuB displacement to reduce Fe(III) for transport by FetM. Together, these data indicate that FetMP is an additional iron uptake system composed of a putative iron permease and an iron-scavenging and potentially iron-reducing periplasmic protein.