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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.
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