High Resolution Crystal Structure of the Grb2 SH2 Domain with a Phosphopeptide Derived from CD28

• DOI: 10.1371/journal.pone.0074482
• Publication Date: 2013-10-01T03:53:07Z
• Authors: Kunitake Higo; Teikichi Ikura; Masayuki Oda; Hisayuki Morii; Jun Takahashi; Ryo Abe; Nobutoshi Ito
• Keywords: GRB2; Phosphopeptide

Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein (Grb2) specifically recognizes pY-X-N-X, whereas phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding pY site CD28 (pY-M-N-M) by PI3K and Grb2 through their is key step triggers transduction for T cell activation differentiation. In this study, we determined crystal structure complex pY-containing peptide derived from at 1.35 Å resolution. was found adopt twisted U-type conformation, similar to, but distinct type-I β-turn. all previously reported structures, bound adopts β-turn except those proline residue pY+3 position. Molecular modeling also suggests same might very different conformation.