Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet, Huddinge, Sweden.
Cell. 2010 Oct 29;143(3):404-15. doi: 10.1016/j.cell.2010.09.041. Epub 2010 Oct 21.
ZP3, a major component of the zona pellucida (ZP) matrix coating mammalian eggs, is essential for fertilization by acting as sperm receptor. By retaining a propeptide that contains a polymerization-blocking external hydrophobic patch (EHP), we determined the crystal structure of an avian homolog of ZP3 at 2.0 Å resolution. The structure unveils the fold of a complete ZP domain module in a homodimeric arrangement required for secretion and reveals how EHP prevents premature incorporation of ZP3 into the ZP. This suggests mechanisms underlying polymerization and how local structural differences, reflected by alternative disulfide patterns, control the specificity of ZP subunit interaction. Close relative positioning of a conserved O-glycan important for sperm binding and the hypervariable, positively selected C-terminal region of ZP3 suggests a concerted role in the regulation of species-restricted gamete recognition. Alternative conformations of the area around the O-glycan indicate how sperm binding could trigger downstream events via intramolecular signaling.
ZP3 是透明带（ZP）基质涂层哺乳动物卵的主要成分，作为精子受体对于受精至关重要。通过保留含有聚合阻断外部疏水区（EHP）的前肽，我们以 2.0Å 的分辨率确定了 ZP3 的一种禽类同源物的晶体结构。该结构揭示了分泌所需的完整 ZP 结构域模块的折叠，以及 EHP 如何防止 ZP3 过早掺入 ZP。这表明了聚合的机制，以及局部结构差异（反映在替代的二硫键模式中）如何控制 ZP 亚基相互作用的特异性。对于精子结合很重要的保守 O-聚糖和 ZP3 的高度可变、正选择的 C 末端区域的紧密相对定位表明，它们在调节种间配子识别方面具有协同作用。O-聚糖周围区域的替代构象表明，精子结合如何通过分子内信号触发下游事件。
