3WA4

Grb2 SH2 domain/CD28-derived peptide complex

Summary for 3WA4

• Entry DOI: 10.2210/pdb3wa4/pdb
• Descriptor: Growth factor receptor-bound protein 2, T-cell-specific surface glycoprotein CD28, CADMIUM ION, ... (5 entities in total)
• Functional Keywords: grb2 sh2 domain, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P62993; Membrane; Single-pass type I membrane protein: P10747
• Total number of polymer chains: 2
• Total formula weight: 12582.32

Authors

Higo, K.,Oda, M.,Ito, N. (deposition date: 2013-04-23, release date: 2014-02-26, Last modification date: 2024-10-16)

Primary citation

Higo, K.,Ikura, T.,Oda, M.,Morii, H.,Takahashi, J.,Abe, R.,Ito, N.
High Resolution Crystal Structure of the Grb2 SH2 Domain with a Phosphopeptide Derived from CD28
Plos One, 8:e74482-e74482, 2013

PubMed Abstract: 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 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

PubMed: 24098653
DOI: 10.1371/journal.pone.0074482

Experimental method

X-RAY DIFFRACTION (1.35 Å)