An elastic element in the protocadherin-15 tip link of the inner ear

摘要: Tip link filaments convey force and gate inner-ear hair-cell transduction channels to mediate perception of sound head movements. Cadherin-23 protocadherin-15 form tip links through a calcium-dependent interaction their extracellular domains made multiple cadherin (EC) repeats. These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved calcium-binding sites that confer mechanical strength them. Here we present the X-ray crystal structures human EC8-EC10 mouse EC9-EC10, which show an EC8-9 canonical-like linker, EC9-10 calcium-free linker alters linear arrangement EC Molecular dynamics simulations small-angle scattering experiments support this non-linear conformation. Simulations also suggest unbending confers some elasticity otherwise rigid links. The new structure provides first view protocadherin-15's non-canonical suggests how they may function mechanotransduction, implications for other cadherins.