Cation-responsive cavity expansion of valinomycin revealed by cryogenic ion trap infrared spectroscopy.

Valinomycin (VM) is a natural K + -selective ionophore that transports K + through the cell membrane. VM captures K + in its central cavity with a C 3 -symmetric β-turn-like backbone. Although the binding affinity is drastically decreased for the VM-sodium (Na + VM) complex with respect to K + VM, VM holds relatively high affinity to Rb + and Cs + . The high affinity for larger ions irrespective of ionic size seems to conflict with the expected optimal size matching model and raises questions on what factors determine ion selectivity. A combination of infrared spectroscopy with supporting computational calculations reveals that VM can accommodate larger Rb + and Cs + by flexibly changing its cavity size with the elongation of its folded β-turn-like backbone. The high affinity to Rb + and Cs + can be ascribed to a size-dependent cavity expansion. These findings provide a new perspective on molecular recognition and selectivity beyond the conventional size matching model.