Correlation between Dynamics and High Affinity Binding in an SH2 Domain Interaction

Citations Over TimeTop 10% of 1996 papers

Abstract

Protein-protein interfaces can consist of interactions between large numbers of residues of each molecule; some of these interactions are critical in determining binding affinity and conferring specificity, while others appear to play only a marginal role. Src-homology-2 (SH2) domains bind to proteins containing phosphorylated tyrosines, with additional specificity provided by interactions with residues C-terminal to the phosphotyrosine (pTyr) residue. While the C-terminal SH2 domain of phospholipase C-gamma 1 (PLCC SH2) interacts with eight residues of a pTyr-containing peptide from its high affinity binding site on the beta-platelet-derived growth factor receptor, it can still bind tightly to a phosphopeptide containing only three residues. Novel deuterium (2H) based nuclear magnetic resonance (NMR) spin relaxation experiments which probe the nanosecond-picosecond time scale dynamics of methyl containing side chain residues have established that certain regions of the PLCC SH2 domain contacting the residues C-terminal to the pTyr have a high degree of mobility in both the free and peptide complexed states. In contrast, there is significant restriction of motion in the pTyr binding site. These results suggest a correlation between the dynamic behavior of certain groups in the PLCC SH2 complex and their contribution to high affinity binding and binding specificity.

Related Papers

• → Phosphatidylinositol 3-kinase p85 SH2 domain specificity defined by direct phosphopeptide/SH2 domain binding(1993)165 cited
• → Specificity and regulation of phosphotyrosine signaling through SH2 domains(2020)35 cited
• → Design and characterization of non-Phosphopeptide inhibitors for Src family SH2 domains(2002)15 cited
• Regulation of c-Src tyrosine kinase activity by the Src SH2 domain.(1993)
• → Multiple SH2-mediated interactions in v-src-transformed cells.(1992)53 cited