Töpfer-Petersen E, Romero A, Varela P F, Ekhlasi-Hundrieser M, Dostàlovà Z, Sanz L, Calvete J J
Institut für Reproduktionsmedizin, Tierärzttliche Hochschule Hannover, Germany.
Andrologia. 1998 Aug-Sep;30(4-5):217-24. doi: 10.1111/j.1439-0272.1998.tb01163.x.
Spermadhesins are a novel family of secretory proteins expressed in the male genital tract of pig, horse and bull. They are major products of the seminal plasma and have been found to be peripherally associated to the sperm surface. The structure and function of spermadhesins have been thoroughly investigated in the pig, which exhibits the greatest diversity of members: AWN, AQN-1, AQN-2, PSP-I and PSP-II and its glycosylated isoforms. They are multifunctional proteins showing a range of ligand-binding abilities, e.g. carbohydrates, sulfated glycosaminoglycans, phospholipids and protease inhibitors, suggesting that they may be involved in different steps of fertilization. Isolated porcine spermadhesins bind the zona pellucida glycoproteins in a cation-dependent manner with a Kd in a low micromolar range, and AWN, AQN-1 and AQN-3 display similar binding affinity for glycoproteins containing Gal beta(1-3)-GalNAc and Gal beta(1-4)-GlcNAc sequences in O-linked and N-linked oligosaccharides, respectively. During sperm passage through the epididymis AQN-3 and AWN have been shown to bind tightly to the sperm surface by interaction with the phospholipids of the membrane bilayer. At ejaculation the spermadhesins form a protective coat around the sensitive acrosomal region of the sperm head, thus possibly preventing premature acrosome reaction. During in vitro capacitation most of these aggregated sperm adhesins are lost, with the exception of phospholipid-bound spermadhesins. AWN and AQN-3 may now serve as a primary receptor for the oocyte zona pellucida, thus contributing to initial binding and recognition between sperm and egg. The amino acid sequence of spermadhesins does not show any discernible similarity with known carbohydrate recognition domains (CRD). However, they belong to the superfamily of proteins with a CUB domain with a predicted all-beta structure. The crystal structure of the heterodimeric complex of the spermadhesins PSP-I/PSP-II has been solved, showing that the overall structure of both spermadhesins consists of a beta-sandwich with five (parallel and antiparallel) beta-strands. It is the first three-dimensional structure of a zona pellucida-binding protein and reveals the architecture of the CUB domain. The spermadhesins represent a novel class of lectins that may be involved in sequential steps of fertilization, at least in the pig.
精子黏附素是在猪、马和公牛的雄性生殖道中表达的一类新型分泌蛋白。它们是精浆的主要成分，已发现与精子表面外周相关。精子黏附素的结构和功能在猪身上得到了深入研究，猪的精子黏附素成员种类最为多样：AWN、AQN - 1、AQN - 2、PSP - I和PSP - II及其糖基化异构体。它们是多功能蛋白质，具有一系列配体结合能力，如碳水化合物、硫酸化糖胺聚糖、磷脂和蛋白酶抑制剂，这表明它们可能参与受精的不同步骤。分离出的猪精子黏附素以阳离子依赖的方式结合透明带糖蛋白，解离常数在低微摩尔范围内，并且AWN、AQN - 1和AQN - 3分别对O - 连接和N - 连接寡糖中含有Galβ(1 - 3)-GalNAc和Galβ(1 - 4)-GlcNAc序列的糖蛋白表现出相似的结合亲和力。在精子通过附睾的过程中，AQN - 3和AWN已被证明通过与膜双层的磷脂相互作用而紧密结合在精子表面。射精时，精子黏附素在精子头部敏感的顶体区域周围形成一层保护膜，从而可能防止顶体过早反应。在体外获能过程中，除了与磷脂结合的精子黏附素外，大多数这些聚集的精子黏附素会丢失。AWN和AQN - 3现在可能作为卵母细胞透明带的主要受体，从而有助于精子与卵子之间的初始结合和识别。精子黏附素的氨基酸序列与已知的碳水化合物识别结构域（CRD）没有任何明显的相似性。然而，它们属于具有预测的全β结构的含CUB结构域的蛋白质超家族。精子黏附素PSP - I/PSP - II异二聚体复合物的晶体结构已被解析，表明两种精子黏附素的整体结构均由一个具有五条（平行和反平行）β链的β折叠组成。这是透明带结合蛋白的第一个三维结构，揭示了CUB结构域的结构。精子黏附素代表了一类新型凝集素，至少在猪中可能参与受精的连续步骤。
