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 alpha-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.
Candel
Adela M
AM
Departamento de Química Física e Instituto de Biotecnología, Facultad de Ciencias, Universidad de Granada, Campus Fuentenueva s/n, 18071 Granada, Spain.
Conejero-Lara
Francisco
F
Martinez
Jose C
JC
van Nuland
Nico A J
NA
Bruix
Marta
M
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019277:Entropy; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry / Q000187:drug effects; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D013049:Spectrin / Q000737:chemistry*; D018909:src Homology Domains
D003432:Cross-Linking Reagents; D008024:Ligands; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013049:Spectrin