The ZP domain is a conserved module for polymerization of extracellular proteins
The ZP domain is a conserved module for polymerization of extracellular proteins
复制标题
DOI：
10.1038/ncb802
复制
发表时间：
2002-06-01
影响因子：
21.3
通讯作者：
Wassarman, PM
中科院分区：
文献类型：
--
作者：
Jovine, L;Qi, HY;Wassarman, PM
许多真核细胞外蛋白共享一个未知功能序列，称为透明带（ZP）结构域(1)。这些蛋白包括哺乳动物精子受体ZP2和ZP3、非哺乳动物卵膜蛋白、Tamm-Horsfall蛋白（THP）、糖蛋白-2 （GP-2）、α -和β -tectorins、转化生长因子(TGF)- β受体III和内啡肽、DMBT-1（在恶性脑肿瘤中缺失-1）、NompA （no-mechanoreceptor-potential-A）、Dumpy和cuticlin1（参考文献1,2）。在这里，我们报道了ZP2， ZP3和THP的ZP结构域负责将这些蛋白质聚合成具有相似超分子结构的细丝。大多数ZP结构域蛋白是作为羧基末端跨膜结构域或糖基磷脂酰肌醇（GPI）锚定体的前体合成的（1,2）。我们的研究结果表明，ZP2和ZP3的c端跨膜结构域和短胞质尾不是分泌所必需的，而是组装所必需的。最后，我们提出了由α -护甲素ZP结构域点突变引起的显性人类听力障碍的分子基础（3-5）。
Many eukaryotic extracellular proteins share a sequence of unknown function, called the zona pellucida (ZP) domain(1). 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 (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(1,2). 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(3-5).