Lipoprotein MtsA of MtsABC in Streptococcus pyogenes primarily binds ferrous ion with bicarbonate as a synergistic anion

Abstract 

Lipoprotein MtsA is a critical component of MtsABC responsible for iron binding and transport in the Gram-positive bacterium Streptococcus pyogenes. The present collective experimental data establish that Fe²⁺ is the primary binding ion for MtsA under optimal physiologically relevant conditions. The binding affinities of MtsA to metal ions are Fe²⁺>Fe³⁺>Cu²⁺>Mn²⁺>Zn²⁺. We report for the first time that bicarbonate is required as a synergistic anion for stable ferrous binding to MtsA, similar to the iron binding in human transferrin. This work provides valuable information, which helps to understand iron metabolism in bacteria, and creates a basis for developing strategies to suppress bacterial infection.

Abbreviations: ABC, ATP binding cassette, E. coli, Escherichia coli, ICP-MS, inductively coupled plasma mass spectroscopy, IPTG, isopropyl β-d-thiogalactoside, MALDI, matrix-assisted laser-desorption ionization, NMR, nuclear magnetic resonance, PMF, peptide-mass-fingerprinting, S. pneumoniae, Streptococcus pneumonia, S. pyogenes, Streptococcus pyogenes

Keywords: MtsA, Ferrous ion, Bicarbonate, Metal binding, Streptococcus pyogenes