The GYF domain is a novel structural fold that is involved in lymphoid signaling through proline-rich sequences

T cell activation through the CD2 cell surface receptor is transmitted by p roline-rich sequences within its cytoplasmic tail. A membrane-proximal prol ine-rich tandem repeat, involved in cytokine production, is recognized by t he intracellular CD2 binding protein CD2BP2. We solved the solution structu re of the CD2 binding domain of CD2BP2, which we name the glycine-tyrosine- phenylalanine (GYF) domain. The GYF sequence is part of a structurally uniq ue bulge-helix-bulge motif that constitutes the major binding site for the CD2 tail. A hydrophobic surface patch is created by motif residues that are highly conserved among a variety of proteins from diverse eukaryotic speci es. Thus, the architecture of the GYF domain may be widely used in protein- protein associations.