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
It tethers vesicles to the plasma membrane, facilitating sound encoding. tm,cc,jp
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
This guide focuses on the molecular mechanism of otoferlin-mediated vesicle docking and Ca 2+raised to the 2 plus power sensing in inner hair cells (IHCs). Role: Otoferlin acts as a key Ca 2+raised to the 2 plus power sensor for synaptic vesicle fusion in auditory IHCs. The protein utilizes C2 domains to bridge synaptic
Sensing: The C2D domain is identified as critical, as disruptions in this area alter synaptic sound encoding.
The protein utilizes C2 domains to bridge synaptic vesicles to the plasma membrane (plasma membrane being the "target membrane").
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