Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats
Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats
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DOI：
10.1038/nature07599
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发表时间：
2008-12-04
期刊：
影响因子：
64.8
通讯作者：
Jovine, Luca
中科院分区：
文献类型：
--
作者：
Monne, Magnus;Han, Ling;Jovine, Luca
卵细胞外基质（透明质酸）和精子之间的物种特异性识别是哺乳动物受精的第一个关键步骤（1）。透明带细丝成分ZP 3和ZP 2作为精子受体，缺乏相应基因的小鼠产生没有透明带的卵母细胞，并且完全不育（2）。与它们在非哺乳动物卵的卵黄包膜和许多其他分泌的真核蛋白中的对应物一样，透明质酸亚基使用“透明质酸（ZP）结构域”模块（3-5），其保守的氨基末端部分（ZP-N）被认为构成其自身的结构域（6）。ZP结构域蛋白的原子结构尚未报道，并且没有关于任何对受精至关重要并直接参与卵-精子结合的保守脊椎动物蛋白的结构信息。在这里，我们描述了2.3埃（埃）分辨率结构的ZP-N片段的小鼠初级精子受体ZP 3。ZP-N折叠定义了一种新的免疫球蛋白超家族亚型，其具有以E'链和涉及聚合的不变酪氨酸残基为特征的β-折叠延伸。该结构强烈支持ZP 2和其他脊椎动物透明卵/卵黄包膜蛋白的N-末端区域内存在ZP-N重复序列，这暗示了整个卵被结构、受精后对多精受精和物种形成的阻断.而且，它为理解ZP结构域蛋白突变引起的人类疾病和开发非激素避孕的新方法提供了重要框架。
Species- specific recognition between the egg extracellular matrix ( zona pellucida) and sperm is the first, crucial step of mammalian fertilization(1). Zona pellucida filament components ZP3 and ZP2 act as sperm receptors, and mice lacking either of the corresponding genes produce oocytes without a zona pellucida and are completely infertile(2). Like their counterparts in the vitelline envelope of non- mammalian eggs and many other secreted eukaryotic proteins, zona pellucida subunits polymerize using a 'zona pellucida ( ZP) domain' module(3-5), whose conserved amino- terminal part (ZP-N) was suggested to constitute a domain of its own(6). No atomic structure has been reported for ZP domain proteins, and there is no structural information on any conserved vertebrate protein that is essential for fertilization and directly involved in egg - sperm binding. Here we describe the 2.3 angstrom (angstrom) resolution structure of the ZP-N fragment of mouse primary sperm receptor ZP3. The ZP- N fold defines a new immunoglobulin superfamily subtype with a beta-sheet extension characterized by an E' strand and an invariant tyrosine residue implicated in polymerization. The structure strongly supports the presence of ZP- N repeats within the N- terminal region of ZP2 and other vertebrate zona pellucida/ vitelline envelope proteins, with implications for overall egg coat architecture, the post- fertilization block to polyspermy and speciation. Moreover, it provides an important framework for understanding human diseases caused by mutations in ZP domain proteins and developing new methods of non- hormonal contraception.