Protein 4.1G binds to a unique motif within the Fc gamma RI cytoplasmic tail.
The C-terminal domain of protein 4.1G was identified to interact with the cytosolic tail of the high affinity IgG receptor, Fc gamma RI, 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 Fc gamma RI 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 Fc gamma RI is provided by examining Fc gamma RI-CY-truncated and alanine-substituted mutants. These pointed to an Fc gamma RI 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.
Beekman
Jeffrey M
JM
Immunotherapy Laboratory, Department of Immunology, University Medical Center, Utrecht, The Netherlands.
Bakema
Jantine E
JE
van der Poel
Cees E
CE
van der Linden
Joke A
JA
van de Winkel
Jan G J
JG
Leusen
Jeanette H W
JH
D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D011994:Recombinant Proteins; C028841:erythrocyte membrane band 4.1 protein