Recognition of proline-rich motifs by protein-protein-interaction domains

摘要

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 praline-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.