Protein 4.1G binds to a unique motif within the Fc-gamma RI cytoplasmic tail

Abstract The C-terminal domain of protein 4.1G was identified to interact with the cytosolic tail of the high affinity IgG receptor, FcγRI, in yeast two-hybrid screens. Proteins of the 4.1 family have previously been found to mediate receptor/cytoskeleton interactions. In the study presented here, we show an alternatively spliced 4.1G product to be associated with increased FcγRI binding in yeast two-hybrid assays, and to be selectively enriched in most immune cells at the transcript level. In addition, a detailed analysis of the 4.1G ‘docking site’ within FcγRI is provided by examining FcγRI-CY-truncated and alanine-substituted mutants. These pointed to an FcγRI membrane-proximal core motif of HxxBxxxBB (H represents hydrophobic residues, B basic residues and x represents any residue), followed by hydrophobic and (potentially) negatively charged residues to be central for interaction with protein 4.1G.