Structural basis of ZP2-targeted female nonhormonal contraception

• 成果类型: Article
• 署名作者: Dioguardi, Elisa; Stsiapanava, Alena; Fahrenkamp, Eileen; Han, Ling; de Sanctis, Daniele; Inzunza, Jose; Jovine, Luca
• 署名单位: Karolinska Institutet; Karolinska Institutet; Chiesi Pharmaceuticals Inc
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11490
• DOI: 10.1073/pnas.2426057122
• 发表日期: 2025-04-15
• 关键词: zona-pellucida protein; monoclonal-antibodies; sulfated glycoprotein; fertilization; RECOGNITION; zp2

摘要

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.