Hearing is a mechanical and neurochemical process, which occurs in the hair cells of inner ear that converts the sound vibrations into electrical signals transmitted to the brain. The multi-PDZ scaffolding protein whirlin plays a critical role in the formation and function of stereocilia exposed at the surface of hair cells. In this article, we reported seven stereociliary proteins that encode PDZ binding motifs (PBM) and interact with whirlin PDZ3, where four of them are first reported. We solved the atomic resolution structures of complexes between whirlin PDZ3 and the PBMs of myosin 15a, CASK, harmonin a1 and taperin. Interestingly, the PBM of CASK and taperin are rare non-canonical PBM, which are not localized at the extreme C terminus. This large capacity to accommodate various partners could be related to the distinct functions of whirlin at different stages of the hair cell development.

听力是一种机械和神经化学过程，发生在内耳的毛细胞中，将声音振动转换为电信号并传输到大脑。多PDZ支架蛋白旋转蛋白在暴露于毛细胞表面的立体纤毛的形成和功能中起关键作用。在本文中，我们报告了七个编码PDZ结合基序（PBM）并与whirlin PDZ3相互作用的立体纤毛蛋白，其中首次报道了其中的四个。我们解决了旋风蛋白PDZ3与肌球蛋白15a，CASK，谐和蛋白a1和Taperin的PBM之间的复合物的原子拆分结构。有趣的是，CASK和Taperin的PBM是罕见的非规范PBM，它们不位于极端C末端。