Is FeoB the Missing Link in GPCR Evolution?

Science's STKE  17 Dec 2002:
Vol. 2002, Issue 163, pp. tw470-TW470
DOI: 10.1126/stke.2002.163.tw470

Bacteria do not appear to possess the seven transmembrane guanosine triphosphate (GTP)-binding G protein-coupled receptors (GPCRs) that represent one of the largest classes of receptors found in eukaryotes. Marlovits et al. provide evidence that FeoB, a protein required for iron uptake, may have a G protein within the primary sequence of this polytopic transmembrane protein. The NH2 domain contains a consensus guanine nucleotide-binding site with motifs consistent with GTPase activity. In vitro, this domain was able to bind and hydrolyze GTP specifically, with no apparent activity or binding affinity for adenosine triphosphate (ATP). Elimination of guanine nucleotide binding by a point mutation produced a protein that could not restore iron uptake in FeoB-deficient bacteria, confirming the physiological importance of GTP binding. Iron transport is known to be ATP-dependent. Thus, the G protein component of FeoB may serve as a regulator for an ATP-dependent secondary protein that is the transporter or that controls the transporter's activity. The authors further suggest that FeoB may be the "missing link in the evolution of G protein-coupled membrane processes in higher organisms."

T. C. Marlovits, W. Haase, C. Herrmann, S. G. Aller, V. M. Unger, The membrane protein FeoB contains an intramolecular G protein essential for Fe(II) uptake in bacteria. Proc. Natl. Acad. Sci. U.S.A. 99, 16243-16248 (2002). [Abstract] [Full Text]