Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor

• Main Authors: Meadows, Robert P., Logan, Timothy M., Wade, Warren S., Ravichandran, Kodimangalam S., Burakoffe, Steven J., Fesik, Stephen W., Zhou, Ming-Ming, Yoon, Ho Sup
• Other Authors: School of Biological Sciences
• Format: Conference or Workshop Item
• Language: English
• Published: 2012
• Subjects: DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/94261; http://hdl.handle.net/10220/7506
• Institution: Nanyang Technological University

Shc is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and has been implicated in coupling the stimulation of growth factor, cytokine, and antigen receptors to the Ras signaling pathway. She interacts with several tyrosine-phosphorylated receptors through its C-terminal SH2 domain, and one of the mechanisms of T-cell receptor-mediated Ras activation involves the interaction of the Shc SH2 domain with the tyrosine-phosphorylated zeta chain of the T-cell receptor. Here we describe a high-resolution NMR structure of the Shc SH2 domain complexed to a phosphopeptide (GHDGLpYQGLSTATK) corresponding to a portion of the zeta chain of the T-cell receptor. Although the overall architecture of the protein is similar to other SH2 domains, distinct structural differences were observed in the smaller beta-sheet, BG loop, (pY + 3) phosphopeptide-binding site, and relative position of the bound phosphopeptide.