9H4S

Structure of fertilization-blocking monoclonal antibody IE-3 VHVL bound to the ZP-N1 domain of mouse ZP2 (crystal form II)

Summary for 9H4S

• Entry DOI: 10.2210/pdb9h4s/pdb
• Related: 5II6 8RKE 8RKF 9H4R
• Descriptor: Zona pellucida sperm-binding protein 2, Heavy chain variable (VH) domain of anti-ZP2 monoclonal antibody IE-3, Light chain variable (VL) domain of anti-ZP2 monoclonal antibody IE-3, ... (4 entities in total)
• Functional Keywords: zona pellucida, zp2, zp-n domain, zp-n1 domain, zp module, zp domain, egg-sperm recognition, gamete interaction, immunocontraception, monoclonal antibody, ie-3, ie3, heavy chain variable domain, light chain variable domain, cell adhesion
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 78264.75

Authors

Dioguardi, E.,De Sanctis, D.,Jovine, L. (deposition date: 2024-10-21, release date: 2025-03-12, Last modification date: 2025-04-23)

Primary citation

Dioguardi, E.,Stsiapanava, A.,Fahrenkamp, E.,Han, L.,de Sanctis, D.,Inzunza, J.,Jovine, L.
Structural basis of ZP2-targeted female nonhormonal contraception.
Proc.Natl.Acad.Sci.USA, 122:e2426057122-e2426057122, 2025

PubMed 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.

PubMed: 40215272
DOI: 10.1073/pnas.2426057122

Experimental method

X-RAY DIFFRACTION (2.02 Å)