Structural Basis of Egg Coat-Sperm Recognition at Fertilization

Cell. 2017 Jun 15;169(7):1315-1326.e17. doi: 10.1016/j.cell.2017.05.033.


Recognition between sperm and the egg surface marks the beginning of life in all sexually reproducing organisms. This fundamental biological event depends on the species-specific interaction between rapidly evolving counterpart molecules on the gametes. We report biochemical, crystallographic, and mutational studies of domain repeats 1-3 of invertebrate egg coat protein VERL and their interaction with cognate sperm protein lysin. VERL repeats fold like the functionally essential N-terminal repeat of mammalian sperm receptor ZP2, whose structure is also described here. Whereas sequence-divergent repeat 1 does not bind lysin, repeat 3 binds it non-species specifically via a high-affinity, largely hydrophobic interface. Due to its intermediate binding affinity, repeat 2 selectively interacts with lysin from the same species. Exposure of a highly positively charged surface of VERL-bound lysin suggests that complex formation both disrupts the organization of egg coat filaments and triggers their electrostatic repulsion, thereby opening a hole for sperm penetration and fusion.

Keywords: X-ray crystallography; biological evolution; fertilization; protein interaction domains and motifs; sperm-ovum interactions; zona pellucida; zona pellucida glycoproteins.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Evolution
  • Egg Proteins / chemistry
  • Egg Proteins / metabolism
  • Fertilization*
  • Humans
  • Invertebrates / chemistry
  • Invertebrates / genetics
  • Invertebrates / physiology*
  • Male
  • Models, Molecular
  • Mucoproteins / chemistry
  • Mucoproteins / metabolism
  • Ovum / chemistry
  • Ovum / metabolism
  • Sequence Alignment
  • Species Specificity
  • Spermatozoa / chemistry
  • Spermatozoa / metabolism
  • Vertebrates / genetics
  • Vertebrates / physiology*
  • X-Ray Diffraction
  • Zona Pellucida Glycoproteins / chemistry
  • Zona Pellucida Glycoproteins / metabolism


  • Egg Proteins
  • Mucoproteins
  • Zona Pellucida Glycoproteins
  • lysin, gastropoda