Conformational dynamics promote binding diversity of dynein light chain LC8

► LC8 partners are grouped as those whose binding is enthalpically favored and those whose binding is entropically favored. ► Changes in LC8 flexibility upon binding are peptide dependent. ► Binding of some peptides rigidifies the binding groove, while others do not change the dynamics of the free protein. ► The change in total entropy measured by ITC correlates with the NMR-determined changes in LC8 backbone heterogeneity. ► The dynamical properties retained by the peptide and by the LC8 pocket compensate for lack of crucial conserved interactions.