PTB or not PTB – that is the question

Phosphotyrosine binding (PTB) domains are structurally conserved modules found in proteins involved in numerous biological processes including signaling through cell-surface receptors and protein trafficking. While their original discovery is attributed to the recognition of phosphotyrosine in the context of NPXpY sequences – a function distinct from that of the classical src homology 2 (SH2) domain – recent studies show that these protein modules have much broader ligand binding specificities. These studies highlight the functional diversity of the PTB domain family as generalized protein interaction domains, and reinforce the concept that evolutionary changes of structural elements around the ligand binding site on a conserved structural core may endow these protein modules with the structural plasticity necessary for functional versatility.