Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization

The mouse zona pellucida glycoprotein, mZP2, is thought to be the secondary receptor on eggs for retention of acrosome-reacted sperm during fertilizat ion. Here, we present evidence that one of its complementary binding protei ns on sperm is proacrosin/acrosin. mZP2 binds to proacrosin null sperm cons iderably less effectively than to wild-type sperm. Binding is mediated by a strong ionic interaction between polysulphate groups on mZP2 and basic res idues on an internal proacrosin peptide. The stereochemistry of both sulpha te groups and basic amino acids determines the specificity of binding. Stru cturally relevant sulphated polymers and suramin, a polysulphonated antican cer drug, compete with mZP2 for complementary binding sites on proacrosin/a crosin in solid-phase binding assays. The same competitors also displace at tached sperm from the zona pellucida of eggs in an in vitro fertilization s ystem. This combination of genetic, biochemical and functional data support s the hypothesis that mZP2-proacrosin interactions are important for retent ion of acrosome-reacted sperm on the egg surface during fertilization. Safe mimetics of suramin have potential as non-steroidal antifertility agents.