哺乳动物受精过程（遵循两个物种都必需有特异性、且一个精子对一个卵子的准则）的第一步是，包裹卵子的膜（称之为卵膜）中的外壳蛋白与精子之间的识别。小鼠卵膜蛋白ZP3是精子的主要受体，而且其最保守区域(ZP-N)也见于具有一系列生物功能的数百种不同细胞外蛋白中。现在，ZP3的ZP-N区域的晶体结构已被确定。ZP-N采取一个免疫球蛋白一样的折叠方式，但与其他免疫球蛋白区域几乎没有相似之处，这使其成为这一超级家族的一个新亚型。除了使我们能够有机会以原子分辨率一瞥哺乳动物受精过程之外，ZP3 ZP-N的结构对于生殖医学研究、对于诸如非症候耳聋或肾脏和血管疾病等（这些疾病中也涉及含ZP-N的蛋白）的研究也有参考意义。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 456, 653-657 (4 December 2008) | doi:10.1038/nature07599
Crystal structure of the ZP-N domain of ZP3 reveals the core fold of animal egg coats
Magnus Monné1,2, Ling Han1,2, Thomas Schwend1, Sofia Burendahl1 & Luca Jovine1
1 Karolinska Institutet, Department of Biosciences and Nutrition, H?lsov?gen 7, SE-141 57 Huddinge, Sweden
2 These authors contributed equally to this work.
Species-specific recognition between the egg extracellular matrix (zona pellucida) and sperm is the first, crucial step of mammalian fertilization1. 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 infertile2. 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' module3, 4, 5, whose conserved amino-terminal part (ZP-N) was suggested to constitute a domain of its own6. 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 ångström (Å) 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 β-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.
