How a single sperm protein recognizes highly divergent egg coat components

Abstract

For successful fertilization, sperm must recognize and penetrate the egg coat, called vitelline envelope (VE) or, in mammals, zona pellucida (ZP). In abalone, sperm acrosomal protein lysin dissolves the VE by binding the N-terminal region of egg coat subunit VERL, encompassing 22 ZP-N domains (VR1-22), but how sperm engages other VE components remains unclear. Here we report free and lysin-bound structures of VEZP14-N1, the single ZP-N repeat of VERL paralog VEZP14, together with biochemical and biophysical data. Despite [~]20% sequence identity to VRs, VEZP14-N1 presents a structurally equivalent surface to lysin, indicating that conserved interaction geometry underlies recognition. Binding is asymmetric: lysin is conformationally rigid, whereas VEZP14-N1 requires homodimer dissociation and induced-fit rearrangements to bind -- kinetic costs that limit affinity to an intermediate level, consistent with a decoy role sequestering lysin from VERL. These findings illuminate how one sperm protein binds divergent egg coat targets, with implications for ZP-N repeat function in vertebrate gamete recognition.