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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

Otoferlin engages the target membrane specifically through a large interface involving the N-terminal C2B and C-terminal C2F-C2G domains . Ca 2+raised to the 2 plus power tm,cc,jp

The protein utilizes C2 domains to bridge synaptic vesicles to the plasma membrane (plasma membrane being the "target membrane"). Lack of functional otoferlin or its C2 domain

The protein utilizes several C2 domains (C2A-C2F) to bind Ca 2+raised to the 2 plus power and lipids, as shown in the protein structure below. 2. C2 Domains: Function & Interactions The protein utilizes several C2 domains (C2A-C2F) to

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.