Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin

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...

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Main Authors: Xiang Yuan, Yihan Wang, Malik Ahsan Ali, Ziyue Qin, Zhihua Guo, Yan Zhang, Ming Zhang, Guangbin Zhou, Jiandong Yang, Lei Chen, Linyuan Shen, Li Zhu, Changjun Zeng
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/2/1664
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author Xiang Yuan
Yihan Wang
Malik Ahsan Ali
Ziyue Qin
Zhihua Guo
Yan Zhang
Ming Zhang
Guangbin Zhou
Jiandong Yang
Lei Chen
Linyuan Shen
Li Zhu
Changjun Zeng
author_facet Xiang Yuan
Yihan Wang
Malik Ahsan Ali
Ziyue Qin
Zhihua Guo
Yan Zhang
Ming Zhang
Guangbin Zhou
Jiandong Yang
Lei Chen
Linyuan Shen
Li Zhu
Changjun Zeng
author_sort Xiang Yuan
collection DOAJ
description 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 <i>OR2C1</i> 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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spelling doaj.art-725aa7fd190a4ad09538a9b8d9d497cf2023-11-30T22:43:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242166410.3390/ijms24021664Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with HeparinXiang Yuan0Yihan Wang1Malik Ahsan Ali2Ziyue Qin3Zhihua Guo4Yan Zhang5Ming Zhang6Guangbin Zhou7Jiandong Yang8Lei Chen9Linyuan Shen10Li Zhu11Changjun Zeng12Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaHeparin, 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 <i>OR2C1</i> 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.https://www.mdpi.com/1422-0067/24/2/1664olfactory receptor<i>OR2C1</i>heparinboar spermcapacitation
spellingShingle Xiang Yuan
Yihan Wang
Malik Ahsan Ali
Ziyue Qin
Zhihua Guo
Yan Zhang
Ming Zhang
Guangbin Zhou
Jiandong Yang
Lei Chen
Linyuan Shen
Li Zhu
Changjun Zeng
Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
International Journal of Molecular Sciences
olfactory receptor
<i>OR2C1</i>
heparin
boar sperm
capacitation
title Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
title_full Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
title_fullStr Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
title_full_unstemmed Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
title_short Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin
title_sort odorant receptor or2c1 is an essential modulator of boar sperm capacitation by binding with heparin
topic olfactory receptor
<i>OR2C1</i>
heparin
boar sperm
capacitation
url https://www.mdpi.com/1422-0067/24/2/1664
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AT linyuanshen odorantreceptoror2c1isanessentialmodulatorofboarspermcapacitationbybindingwithheparin
AT lizhu odorantreceptoror2c1isanessentialmodulatorofboarspermcapacitationbybindingwithheparin
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