Abstract
Two dodecapeptides belonging to distinct classes of Src homology 3 (SH3) ligands and selected from biased phage display libraries were used to investigate interactions between a specificity pocket in the Src SH3 domain and ligant residues flanking the proline-rich core. The solution structures of c-Src SH3 complexed with these peptides were solved by NMR. In addition to proline-rich, polyproline type II helix-forming core, the class I and II ligands each possesses a flanking sequence that occupies a large pocket between the RT and n-Src loops of the SH3 domain. Structural and mutational analyses illustrate how the two classes of SH3 ligands exploit a specificity pocket on the receptor differently to increase binding affinity and specificity.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing*
-
Amino Acid Sequence
-
Animals
-
Binding Sites
-
Calorimetry
-
Cloning, Molecular
-
DNA Mutational Analysis
-
DNA-Binding Proteins / chemistry*
-
DNA-Binding Proteins / metabolism*
-
GRB2 Adaptor Protein
-
Humans
-
Ligands
-
Magnetic Resonance Spectroscopy
-
Models, Molecular
-
Molecular Sequence Data
-
Mutagenesis
-
Oligopeptides / chemistry
-
Proline*
-
Protein Conformation*
-
Protein Kinases / chemistry*
-
Protein Kinases / metabolism*
-
Protein Structure, Secondary
-
Proteins / chemistry
-
Proteins / metabolism
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / metabolism
-
Sequence Homology, Amino Acid
-
src Homology Domains*
Substances
-
Adaptor Proteins, Signal Transducing
-
DNA-Binding Proteins
-
GRB2 Adaptor Protein
-
GRB2 protein, human
-
Ligands
-
Oligopeptides
-
Proteins
-
Recombinant Proteins
-
Proline
-
Protein Kinases