Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin.
Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin.
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气味受体 OR2C1 是通过与肝素结合实现公猪精子获能的重要调节剂
DOI：
10.3390/ijms24021664
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发表时间：
2023-01-14
影响因子：
5.6
通讯作者：
Zeng, Changjun
中科院分区：
文献类型：
--
作者：
Yuan, Xiang;Wang, Yihan;Ali, Malik Ahsan;Qin, Ziyue;Guo, Zhihua;Zhang, Yan;Zhang, Ming;Zhou, Guangbin;Yang, Jiandong;Chen, Lei;Shen, Linyuan;Zhu, Li;Zeng, Changjun
肝素是一类糖胺聚糖，广泛用于诱导精子获能和受精。肝素如何诱导精子获能仍不清楚。嗅觉受体（ORs）是一种G蛋白偶联受体，被认为与精子获能有关。但ORs与气味分子的相互作用以及ORs介导精子获能的分子机制尚不清楚。本研究旨在探讨肝素与ORs在猪精子获能过程中的相互作用及其机制。结果表明，嗅觉受体2C1（orfactory receptor 2C1，OR2C1）是精子获能的一个必需单位，它通过识别肝素并与肝素结合来调控精子获能。此外，分子动力学（MD）模拟表明，OR2C1与肝素通过疏水空腔结合，该疏水空腔包括Arg3，Ala6，Thr7，Asn171，Arg172，Arg173和Pro287。此外，我们证明了敲低OR2C1显著抑制精子获能。总之，我们强调了一种新的嗅觉受体，OR2C1，在猪精子和肝素的潜在结合，Pro287，在跨膜螺旋区7（TMH7）的保守残基。我们的研究结果将有助于进一步了解OR在精子获能和受精过程中的作用。
Heparin, a class of glycosaminoglycans (GAGs), is widely used to induce sperm capacitation and fertilization. How heparin induces sperm capacitation remains unclear. Olfactory receptors (ORs) which are G protein-coupled receptors, have been proposed to be involved in sperm capacitation. However, the interaction between ORs and odor molecules and the molecular mechanism of ORs mediating sperm capacitation are still unclear. The present study aimed to explore the underlying interaction and mechanism between heparin and ORs in carrying out the boar sperm capacitation. The results showed that olfactory receptor 2C1 (OR2C1) is a compulsory unit which regulates the sperm capacitation by recognizing and binding with heparin, as determined by Dual-Glo Luciferase Assay and molecular docking. In addition, molecular dynamics (MD) simulation indicated that OR2C1 binds with heparin via a hydrophobic cavity comprises of Arg3, Ala6, Thr7, Asn171, Arg172, Arg173, and Pro287. Furthermore, we demonstrated that knocking down OR2C1 significantly inhibits sperm capacitation. In conclusion, we highlighted a novel olfactory receptor, OR2C1, in boar sperm and disclosed the potential binding of heparin to Pro287, a conserved residue in the transmembrane helices region 7 (TMH7). Our findings will benefit the further understanding of ORs involved in sperm capacitation and fertilization.
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