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Adenosine Triphosphate/me [Metabolism] ; Amino Acid Motifs ; Binding Sites ; Catalysis ; Cation Transport Proteins/ch [Chemistry] ; Cation Transport Proteins/ge [Genetics] ; *Cation Transport Proteins/me [Metabolism] ; Escherichia coli/ge [Genetics] ; *Escherichia coli/me [Metabolism] ; Escherichia coli Proteins/ch [Chemistry] ; Escherichia coli Proteins/ge [Genetics] ; *Escherichia coli Proteins/me [Metabolism] ; Evolution, Molecular ; GTP-Binding Proteins/ch [Chemistry] ; GTP-Binding Proteins/ge [Genetics] ; *GTP-Binding Proteins/me [Metabolism] ; Guanosine Diphosphate/me [Metabolism] ; *Guanosine Triphosphate/me [Metabolism] ; Hydrogen Bonding ; Hydrophobicity ; *Iron/me [Metabolism] ; Membrane Proteins/ch [Chemistry] ; Membrane Proteins/ge [Genetics] ; Membrane Proteins/me [Metabolism] ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Substrate Specificity ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S.
Abstract:
G proteins are critical for the regulation of membrane protein function and signal transduction. Nevertheless, coupling between G proteins and membrane proteins with multiple membrane-spanning domains has so far been observed only in higher organisms. Here we show that the polytopic membrane protein FeoB, which is essential for Fe(II) uptake in bacteria, contains a guanine-nucleotide-specific nucleotide binding site. We identify the G4-motif, NXXD, responsible for guanine nucleotide specificity, and show that GTP hydrolysis occurs very slowly. In contrast to typical G proteins, the association and dissociation of GDP were found to be faster than for GTP, suggesting that in the absence of additional factors, FeoB's G protein domain may exist mostly in the GTP-bound form. Furthermore, the binding of GTP is required for efficient Fe(II) uptake through the FeoB-dependent system. Notably, even in bacteria, this covalent linkage between a G protein and a polytopic membrane protein appears, to our knowledge, to be unique. These findings raise the intriguing question whether FeoB represents a primordial archetype of G protein-regulated membrane proteins.
