Iomeprol X-ray contrast media alter conformation and affinity of the ATP binding pocket of actin.

Contrast materials are widely used in various X-ray/CT and MRI diagnostic procedures. When administered in high volumes, contrast agents can strain kidney function and lead to acute renal failure. Contrast materials may damage the plasma membrane and penetrate into tissue cells. Some iodine-based contrast agents have been reported to distort the shape of red blood cells, implying a rearrangement of the actin cytoskeletal network. As actin plays a crucial role in numerous cellular processes, the effects of iodine-based contrast media on actin require clarification. We characterized the effect of iomeprol on the structure and function of actin using calorimetry, co-sedimentation, fluorescence spectroscopy, and molecular docking. Our results revealed that iomeprol disassembles the F-actin network by interacting with G-actin, suggesting a direct influence on its structural and functional properties. In line with this, polymerization and dilution-induced depolymerization assays, as well as critical concentration measurements, showed pronounced effects on actin dynamics. Iomeprol alters the conformation of G-actin, particularly the ATP-binding pocket-which becomes more open-and significantly (∼3-fold) decreases ATP affinity. Molecular docking supported these findings, indicating that iomeprol interacts with the ATP-binding cleft of G-actin. An additional interaction site was identified in the SD1/3 cleft-a known binding site for Wiskott-Aldrich syndrome protein and profilin-suggesting that iomeprol may also influence the association and dissociation dynamics of actin-binding proteins. Overall, our findings indicate that iomeprol can influence the structural and functional properties of actin, raising the possibility that such alterations may contribute to changes in actin organization and, consequently, to actin-dependent cellular processes.