Lack of functional otoferlin or its C2 domain interaction prevents proper vesicle docking, leading to profound deafness. Summary Table: Otoferlin C2 Interactions Function/Location C2B-C2G Main interface for membrane binding C2D Crucial Ca 2+raised to the 2 plus power binding site; mutations affect sound encoding C2F-C2G Rearrange upon membrane binding to close structure Target Membrane Membrane where vesicles are docked

Upon binding, a "closed" conformation is adopted, where C-terminal domains (C2F, C2G) rearrange. 3. Key Findings in Synaptic Transmission Ca 2+raised to the 2 plus power

The binding requires cooperation between multiple C2 domains to secure the vesicle to the target membrane.