Structural and functional analysis of the multi-C2-domain protein otoferlin (A11#)

Otoferlin是ferlin多C2结构域蛋白家族的成员，在内毛细胞的神经递质释放中起关键作用。尽管对内毛细胞中otoferlin功能的理解取得了进展，但仍不清楚多C2结构域如何在突触囊泡胞吐中起作用。利用我们最近在纯化全长otoferlin方面的突破，我们计划解决其生物化学和生物物理特性，并在存在或不存在辅因子（Ca2+，脂质，相互作用蛋白）的情况下确定其三维结构。我们希望这项研究能够对otoferlin介导的胞吐作用的分子机制产生新的见解。

Otoferlin, a member of the ferlin multi C2 domain protein family, plays a key role in neurotransmitter release in inner hair cells. Despite advances in understanding the function of otoferlin in inner hair cells, it remains unclear how the multi C2 domains operate in synaptic vesicle exocytosis. Capitalizing on our recent breakthrough in purification of full-length otoferlin, we plan to address its biochemical and biophysical properties and to determine its three-dimensional structure in the presence or absence of cofactors (Ca2+, lipids, interacting proteins). We expect this research to yield novel insights into the molecular mechanism of otoferlin-mediated exocytosis.