Structural basis of ZP2-targeted female nonhormonal contraception.

Dioguardi, Elisa; Stsiapanava, Alena; Fahrenkamp, Eileen; Han, Ling; de Sanctis, Daniele; Inzunza, José; Jovine, Luca · Proc Natl Acad Sci U S A · 2025

basic_science · Level V

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Abstract

Monoclonal antibody IE-3 prevents mouse fertilization by binding ZP2, a major component of the oocyte-specific zona pellucida (ZP). We show that an IE-3-derived single-chain variable fragment (scFV) is sufficient for blocking fertilization in vitro and determine the structural basis of IE-3/ZP2 recognition. The high affinity of this interaction depends on induced fit of the epitope, offering insights for nonhormonal contraceptive design without off-target effects.

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