Abstract
Protein-protein interactions occurring via the recognition of short peptide sequences by modular interaction domains play a central role in the assembly of signalling protein complexes and larger protein networks that regulate cellular behaviour. In addition to spatial and temporal factors, the specificity of signal transduction is intimately associated with the specificity of many co-operative, pairwise binding events upon which various pathways are built. Although protein interaction domains are usually identified via the recognition code, the consensus sequence motif, to which they selectively bind, they are highly versatile and play diverse roles in the cell. For example, a given interaction domain can bind to multiple sequences that exhibit no apparent identity, and, on the other hand, domains of the same class or different classes may favour a given consensus motif. This promiscuity in ligand selection is typified by the SH3 (Src homology 3) domain and several other interaction modules that commonly recognize proline-rich sequences. Furthermore, interaction domains are highly adaptable, a property that is essential for the evolution of novel pathways and modulation of signalling dynamics. The ability of certain interaction domains to perform multiple tasks, however, poses a challenge for the cell to control signalling specificity when cross-talk between pathways is undesired. Extensive structural and biochemical analysis of many interaction domains in recent years has started to shed light on the molecular basis underlying specific compared with diverse binding events that are mediated by interaction domains and the role affinity plays in affecting domain specificity and regulating cellular signal transduction.