A di-iron protein recruited as an Fe[II] and oxygen sensor for bacterial chemotaxis functions by stabilizing an iron-peroxy species

Proc Natl Acad Sci U S A. 2019 Jul 23;116(30):14955-14960. doi: 10.1073/pnas.1904234116. Epub 2019 Jul 3.

Abstract

Many bacteria contain cytoplasmic chemoreceptors that lack sensor domains. Here, we demonstrate that such cytoplasmic receptors found in 8 different bacterial and archaeal phyla genetically couple to metalloproteins related to β-lactamases and nitric oxide reductases. We show that this oxygen-binding di-iron protein (ODP) acts as a sensor for chemotactic responses to both iron and oxygen in the human pathogen Treponema denticola (Td). The ODP di-iron site binds oxygen at high affinity to reversibly form an unusually stable μ-peroxo adduct. Crystal structures of ODP from Td and the thermophile Thermotoga maritima (Tm) in the Fe[III]2-O2 2-, Zn[II], and apo states display differences in subunit association, conformation, and metal coordination that indicate potential mechanisms for sensing. In reconstituted systems, iron-peroxo ODP destabilizes the phosphorylated form of the receptor-coupled histidine kinase CheA, thereby providing a biochemical link between oxygen sensing and chemotaxis in diverse prokaryotes, including anaerobes of ancient origin.

Keywords: chemoreceptor; molecular evolution; oxygen sensor; phosphatase; signal transduction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Chemotaxis*
  • Histidine Kinase / metabolism
  • Iron / metabolism
  • Iron-Binding Proteins / chemistry
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism*
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Oxygen / metabolism
  • Phylogeny
  • Protein Binding
  • Signal Transduction*
  • Thermotoga maritima / enzymology
  • Thermotoga maritima / genetics
  • Treponema denticola / enzymology
  • Treponema denticola / genetics

Substances

  • Bacterial Proteins
  • Iron-Binding Proteins
  • Iron
  • Oxidoreductases
  • Histidine Kinase
  • Oxygen

Associated data

  • PDB/6R9N
  • PDB/6QWO
  • PDB/6QNM
  • PDB/6QR2