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

Luca Jovine, Huayu Qi, Zev Williams, Eveline Litscher, Paul M. Wassarman

Research output: Contribution to journalArticlepeer-review

271 Scopus citations


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), α- and β-tectorins, transforming growth factor (TGF)-β receptor III and endoglin, DMBT-1 (deletd 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 α-tectorin.

Original languageEnglish (US)
Pages (from-to)457-461
Number of pages5
JournalNature Cell Biology
Issue number6
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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