Insights into Egg Coat Assembly and Egg-Sperm Interaction from the X-Ray Structure of Full-Length ZP3
Insights into Egg Coat Assembly and Egg-Sperm Interaction from the X-Ray Structure of Full-Length ZP3
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DOI：
10.1016/j.cell.2010.09.041
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发表时间：
2010-10-29
期刊：
影响因子：
64.5
通讯作者：
Jovine, Luca
中科院分区：
文献类型：
--
作者：
Han, Ling;Monne, Magnus;Jovine, Luca
ZP3是包被哺乳动物卵子的透明带(ZP)基质的主要成分，是精子受体受精所必需的。通过保留含有阻止聚合的外部疏水补丁(EHP)的前肽，我们在2.0埃分辨率下确定了ZP3的鸟类同系物的晶体结构。该结构揭示了分泌所需的同源二聚体排列中完整的ZP结构域模块的折叠，并揭示了EHP如何防止ZP3过早整合到ZP中。这表明了聚合的潜在机制，以及局部结构差异是如何控制ZP亚单位相互作用的特异性的，这些差异由替代的二硫键模式反映。一个保守的O-糖链对精子结合非常重要，而ZP3的高可变、正向选择的C-末端区域的紧密相对定位表明，ZP3在物种限制性配子识别的调节中发挥了协同作用。O-糖链周围区域的不同构象表明，精子结合如何通过分子内信号触发下游事件。
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 angstrom 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.