The high-resolution NMR structure of a single-chain chimeric protein mimicking a SH3–peptide complex

Here we present the high-resolution NMR structure of a chimera (SPCp41) between α-spectrin SH3 domain and the decapeptide p41. The tertiary structure mimics perfectly the interactions typically found in SH3–peptide complexes and is remarkably similar to that of the complex between the separate Spc-SH3 domain and ligand p41. Relaxation data confirm the tight binding between the ligand and SH3 part of the chimera. This chimera will serve as a tool for a deeper understanding of the relationship between structure and thermodynamics of binding using a combination of NMR, stability and site-directed mutagenesis studies, which can lead to an effective strategy for ligand design.