Structure of Zona Pellucida Module Proteins

Curr Top Dev Biol. 2018:130:413-442. doi: 10.1016/bs.ctdb.2018.02.007. Epub 2018 May 10.


The egg coat, an extracellular matrix made up of glycoprotein filaments, plays a key role in animal fertilization by acting as a gatekeeper for sperm. Egg coat components polymerize using a common zona pellucida (ZP) "domain" module that consists of two related immunoglobulin-like domains, called ZP-N and ZP-C. The ZP module has also been recognized in a large number of other secreted proteins with different biological functions, whose mutations are linked to severe human diseases. During the last decade, tremendous progress has been made toward understanding the atomic architecture of the ZP module and the structural basis of its polymerization. Moreover, sperm-binding regions at the N-terminus of mollusk and mammalian egg coat subunits were found to consist of domain repeats that also adopt a ZP-N fold. This discovery revealed an unexpected link between invertebrate and vertebrate fertilization and led to the first structure of an egg coat-sperm protein recognition complex. In this review we summarize these exciting findings, discuss their functional implications, and outline future challenges that must be addressed in order to develop a comprehensive view of this family of biomedically important extracellular molecules.

Keywords: Endoglin–BMP9 complex; Fertilization; Uromodulin; VERL–lysin complex; X-ray crystallography; ZP domain; ZP module; ZP-C domain; ZP-N domain; ZP1; ZP2; ZP3; ZP4; Zona pellucida.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Female
  • Fertilization / physiology
  • Humans
  • Male
  • Protein Domains
  • Protein Multimerization / physiology
  • Sperm-Ovum Interactions / physiology
  • Zona Pellucida / chemistry
  • Zona Pellucida / metabolism
  • Zona Pellucida Glycoproteins / chemistry*
  • Zona Pellucida Glycoproteins / physiology


  • Zona Pellucida Glycoproteins