The ZP domain is a conserved module for polymerization of extracellular proteins.
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.
Jovine
Luca
L
Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
Qi
Huayu
H
Williams
Zev
Z
Litscher
Eveline
E
Wassarman
Paul M
PM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017124:Conserved Sequence; D006224:Cricetinae; D004527:Egg Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D005110:Extracellular Space / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009088:Mucoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D011108:Polymers / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface; D058949:Uromodulin; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008562:Membrane Glycoproteins; D009088:Mucoproteins; D011108:Polymers; D011956:Receptors, Cell Surface; C548612:UMOD protein, human; C548613:Umod protein, mouse; D058949:Uromodulin; C000606515:ZP2 protein, human; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606520:Zp2 protein, mouse; C000606521:Zp3 protein, mouse