TY - JOUR
T1 - The ZP domain is a conserved module for polymerization of extracelluar proteins
AU - Jovine, Luca
AU - Qi, Huayu
AU - Williams, Zev
AU - Litscher, Eveline
AU - Wassarman, Paul M.
N1 - Funding Information:
ACKNOWLEDGEMENTS We thank F. Serafini-Cessi for advice on THP purification, W.G.M. Janssen for help with EM analysis of THP and J.E. Heuser for imaging of mouse ZP filaments. We are also grateful to R. De Santis for communicating results before publication and to F. Cotelli, M. Paterlini and V. Gusarova for discussion. Confocal laser scanning microscopy was performed at the MSSM-Microscopy Shared Resource Facility; the N-terminal sequence of THP-ZPD was determined at the HHMI/Columbia University Protein Chemistry Core Facility. L.J. is supported by a Human Frontier Science Program long-term fellowship. This research was supported in part by National Institutes of Health grant HD35105. Correspondence and requests for materials should be addressed to P.M.W.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1038/ncb802
DO - 10.1038/ncb802
M3 - Article
C2 - 12021773
AN - SCOPUS:0036307181
SN - 1465-7392
VL - 4
SP - 457
EP - 461
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 6
ER -