Hotel Estoril Eden, Monte Estoril,
Portugal
5-8 October 2005

 

 
 

Text Box: Participants
Text Box: Programme


S
ystematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks

Victor Neduva
European Molecular Biology Laboratory, Germany

Many aspects of cell signalling, trafficking and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or linear motif (e.g. SH3 binding to PxxP). Many domains are known, though comparatively few linear motifs have been discovered.  Their short length (3-8 residues), and the fact that they often reside in disordered regions in proteins makes them difficult to detect through sequence comparison or experiment. Nevertheless, each new motif provides critical molecular details of how interaction networks are constructed, and can explain how one protein is able bind to very different partners. We develop a method that detects binding motifs using data from genome-scale interaction studies, and thus avoid the normally slow discovery process. Our approach based on motif over-representation in non-homologous sequences, re-discovers known motifs and predicts dozens of others. Direct binding experiments reveal that two predicted motifs are indeed protein-binding modules. We estimate that there are dozens or even hundreds of linear motifs yet to be discovered that will give molecular insight into protein networks and greatly illuminate cellular processes.