Recognition of proline-rich motifs by protein-protein-interaction domains.
Protein-protein interactions are essential in every aspect of cellular activity. Multiprotein complexes form and dissociate constantly in a specifically tuned manner, often by conserved mechanisms. Protein domains that bind proline-rich motifs (PRMs) are frequently involved in signaling events. The unique properties of proline provide a mechanism for highly discriminatory recognition without requiring high affinities. We present herein a detailed, quantitative assessment of the structural features that define the interfaces between PRM-binding domains and their target PRMs, and investigate the specificity of PRM recognition. Together with the analysis of peptide-library screens, this approach has allowed the identification of several highly conserved key interactions found in all complexes of PRM-binding domains. The inhibition of protein-protein interactions by using small-molecule agents is very challenging. Therefore, it is important to first pinpoint the critical interactions that must be considered in the design of inhibitors of PRM-binding domains.
Ball
Linda J
LJ
Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany. linda@fmp-berlin.de
Kühne
Ronald
R
Schneider-Mergener
Jens
J
Oschkinat
Hartmut
H
D020816:Amino Acid Motifs; D008024:Ligands; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary
D008024:Ligands; D010455:Peptides; D011392:Proline