A structural view of egg coat architecture and function in fertilization

Biol Reprod. 2011 Oct;85(4):661-9. doi: 10.1095/biolreprod.111.092098. Epub 2011 Jun 29.


Species-restricted interaction between gametes at the beginning of fertilization is mediated by the extracellular coat of the egg, a matrix of cross-linked glycoprotein filaments called the zona pellucida (ZP) in mammals and the vitelline envelope in nonmammals. All egg coat subunits contain a conserved protein-protein interaction module-the "ZP domain"-that allows them to polymerize upon dissociation of a C-terminal propeptide containing an external hydrophobic patch (EHP). Recently, the first crystal structures of a ZP domain protein, sperm receptor ZP subunit zona pellucida glycoprotein 3 (ZP3), have been reported, giving a glimpse of the structural organization of the ZP at the atomic level and the molecular basis of gamete recognition in vertebrates. The ZP module is divided in two related immunoglobulin-like domains, ZP-N and ZP-C, that contain characteristic disulfide bond patterns and, in the case of ZP-C, also incorporate the EHP. This segment lies at the interface between the two domains, which are connected by a long loop carrying a conserved O-glycan important for binding to sperm in vitro. The structures explain several apparently contradictory observations by reconciling the variable disulfide bond patterns found in different homologues of ZP3 as well as the multiple ZP3 determinants alternatively involved in gamete interaction. These findings have implications for our understanding of ZP subunit biogenesis; egg coat assembly, architecture, and interaction with sperm; structural rearrangements leading to postfertilization hardening of the ZP and the block to sperm binding; and the evolutionary origin of egg coats.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dimerization
  • Egg Proteins / chemistry*
  • Egg Proteins / metabolism*
  • Female
  • Fertilization*
  • Humans
  • Male
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism*
  • Protein Conformation
  • Protein Folding
  • Protein Interaction Domains and Motifs
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism*
  • Species Specificity
  • Sperm-Ovum Interactions
  • Vitelline Membrane / metabolism
  • Zona Pellucida / metabolism*
  • Zona Pellucida Glycoproteins


  • Egg Proteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • ZP3 protein, human
  • Zona Pellucida Glycoproteins