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

Abstract

Valinomycin (VM) is a natural K⁺-selective ionophore that transports K⁺ through the cell membrane. VM captures K⁺ in its central cavity with a C₃-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.