The ZP domain is a conserved module for polymerization of extracellular proteins

Nat Cell Biol. 2002 Jun;4(6):457-61. doi: 10.1038/ncb802.


Many eukaryotic extracellular proteins share a sequence of unknown function, called the zona pellucida (ZP) domain. Among these proteins are the mammalian sperm receptors ZP2 and ZP3, non-mammalian egg coat proteins, Tamm-Horsfall protein (THP), glycoprotein-2 (GP-2), alpha- and beta-tectorins, transforming growth factor (TGF)-beta receptor III and endoglin, DMBT-1 (deleted in malignant brain tumour-1), NompA (no-mechanoreceptor-potential-A), Dumpy and cuticlin-1 (refs 1,2). Here, we report that the ZP domain of ZP2, ZP3 and THP is responsible for polymerization of these proteins into filaments of similar supramolecular structure. Most ZP domain proteins are synthesized as precursors with carboxy-terminal transmembrane domains or glycosyl phosphatidylinositol (GPI) anchors. Our results demonstrate that the C-terminal transmembrane domain and short cytoplasmic tail of ZP2 and ZP3 are not required for secretion, but are essential for assembly. Finally, we suggest a molecular basis for dominant human hearing disorders caused by point mutations within the ZP domain of alpha-tectorin.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Conserved Sequence
  • Cricetinae
  • Egg Proteins / chemistry*
  • Egg Proteins / genetics
  • Egg Proteins / metabolism*
  • Evolution, Molecular
  • Extracellular Space / metabolism
  • Gene Deletion
  • Humans
  • Male
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mucoproteins / chemistry*
  • Mucoproteins / genetics
  • Mucoproteins / metabolism*
  • Mutagenesis, Site-Directed / physiology
  • Oocytes / physiology
  • Polymers / metabolism
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Receptors, Cell Surface*
  • Uromodulin
  • Zona Pellucida Glycoproteins


  • Egg Proteins
  • Membrane Glycoproteins
  • Mucoproteins
  • Polymers
  • Receptors, Cell Surface
  • UMOD protein, human
  • Umod protein, mouse
  • Uromodulin
  • ZP2 protein, human
  • ZP3 protein, human
  • Zona Pellucida Glycoproteins
  • Zp2 protein, mouse
  • Zp3 protein, mouse