- The long C terminal tail of the Shaker Kv channel is responsible for scaffold protein-mediated Kv channel clustering, a process important for action potential propagation along the axon and across the synapse. Recently, we have shown that the Shaker B Kv channel tail, harboring the terminal PDZ-binding motif, is intrinsically disordered (ID) and that modification of the ID character of the tail affects PSD-95 binding, as well as channel clustering. A ‘ball-and-chain'-like mechanism was suggested to describe the interaction of the channel's tail with the PDZ domains of the PSD-95 scaffold protein partner. Here, we adopt a polymer chain chemistry approach and demonstrate that systematic shortening of the intrinsically-disordered ShB-C tail results in a monotonic increase in the affinity to its PDZ partner protein. Employing surface plasmon resonance analysis, a linear correlation between the length of the Kv channel tail and the association binding energy to PSD-95 is observed. The analysis further reveals that only the association rate constant, but not the dissociation rate constant, is dependent on chain length. This assertion is further strengthened by isothermal calorimetry analysis of the interaction of PDZ domains with Kv channel tails that differ only in tail length. Thus, the ID tail of the channel controls the entropy of association whereas the PDZ binding motif at the tail's tip controls the interaction enthalpy. These results suggest that the Kv channel tail is an entropic clock that modulates the time for complex formation with the scaffold protein partner. The conceptual inter-molecular ‘ball-and-chain' working model sheds new light on the role of the Shaker A alternative spliced variant that differs from the B variant only in terms of the length of the C terminal tail.