Specificity and affinity motifs for Grb2 SH2-ligand interactions.
Protein-protein interactions are often mediated by the recognition of short continuous amino acid stretches on target proteins by specific binding domains. Affinity-based selection strategies have successfully been used to define recognition motifs for a large series of such protein domains. However, in many biological systems specificity of interaction may be of equal or greater importance than affinity. To address this issue we have developed a peptide library screening technology that can be used to directly define ligands for protein domains based on both affinity and specificity of interaction. We demonstrate the value of this approach by the selection of peptide ligands that are either highly specific for the Grb2 Src homology 2 (SH2) domain or that are cross-reactive between a group of related SH2 domains. Examination of previously identified physiological ligands for the Grb2 SH2 domain suggests that for these ligands regulation of the specificity of interaction may be an important factor for in vivo ligand selection.
Kessels
Helmut W H G
HW
Department of Immunology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Ward
Alister C
AC
Schumacher
Ton N M
TN
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D001483:Base Sequence; D017931:DNA Primers; D051380:GRB2 Adaptor Protein; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D051380:GRB2 Adaptor Protein; D008024:Ligands; D011506:Proteins