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NICOL的化学合成，一种介导哺乳动物雄性生殖道腔内信号传导的共配体分泌蛋白。

Chemical Synthesis of NICOL, A Coligand Secreted Protein Mediating Mammalian Male Reproductive Tract Trans-luminal Signaling.

作者信息

Nagahama Kenta, Takei Toshiki, Ito Shun, Takao Toshifumi, Hojo Hironobu, Kiyozumi Daiji

机构信息

Institute for Protein Research, The University of Osaka, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Research Organization of Science and Technology, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan.

出版信息

Chemistry. 2025 Aug 21;31(47):e01588. doi: 10.1002/chem.202501588. Epub 2025 Jul 26.

DOI:10.1002/chem.202501588
PMID:40713872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12376267/
Abstract

The NELL2-interacting cofactor for lumicrine signaling (NICOL) is a small protein which forms a complex with the neural epidermal growth factor-like like 2 (NELL2) and engaged in sperm maturation in the epididymis. At present, the recombinant expression of NICOL is not efficient, which limits the precise understanding of the structure and function of NICOL. In this study, we first succeeded in the chemical synthesis of NICOL with NELL2 binding affinity. The synthesized NICOL possesses correct SS bond pairing, and its secondary structure is indistinguishable from that of the recombinant protein, indicating that the synthetic NICOL will be useful for structural and functional analyses of lumicrine signaling.

摘要

用于发光信号传导的NELL2相互作用辅助因子（NICOL）是一种小蛋白，它与神经表皮生长因子样蛋白2（NELL2）形成复合物，并参与附睾中的精子成熟过程。目前，NICOL的重组表达效率不高，这限制了对NICOL结构和功能的精确理解。在本研究中，我们首次成功化学合成了具有NELL2结合亲和力的NICOL。合成的NICOL具有正确的二硫键配对，其二级结构与重组蛋白的二级结构无法区分，这表明合成的NICOL将有助于发光信号传导的结构和功能分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/4429be1d7229/CHEM-31-e01588-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/a13e1c239530/CHEM-31-e01588-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/695c0198eb83/CHEM-31-e01588-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/872a9d130b91/CHEM-31-e01588-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/f9bf2b52551b/CHEM-31-e01588-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/718e7f6b5822/CHEM-31-e01588-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/4429be1d7229/CHEM-31-e01588-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/a13e1c239530/CHEM-31-e01588-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/695c0198eb83/CHEM-31-e01588-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/872a9d130b91/CHEM-31-e01588-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/f9bf2b52551b/CHEM-31-e01588-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/718e7f6b5822/CHEM-31-e01588-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a4/12376267/4429be1d7229/CHEM-31-e01588-g001.jpg

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本文引用的文献

1
Expression of NELL2/NICOL-ROS1 lumicrine signaling-related molecules in the human male reproductive tract.NELL2/NICOL-ROS1 发光信号相关分子在男性生殖管道中的表达。
Reprod Biol Endocrinol. 2024 Jan 2;22(1):3. doi: 10.1186/s12958-023-01175-6.
2
Lumicrine signaling: Extracellular regulation of sperm maturation in the male reproductive tract lumen.发光信号：雄性生殖道管腔中精子成熟的细胞外调节。
Genes Cells. 2023 Nov;28(11):757-763. doi: 10.1111/gtc.13066. Epub 2023 Sep 11.
3
A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility.
一种小分泌蛋白 NICOL 调节发光介导的精子成熟和雄性生育力。
Nat Commun. 2023 Apr 24;14(1):2354. doi: 10.1038/s41467-023-37984-x.
4
The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction.附睾的作用和附睾小体对哺乳动物生殖的贡献。
Int J Mol Sci. 2020 Jul 29;21(15):5377. doi: 10.3390/ijms21155377.
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NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility.NELL2 通过 OVCH2 介导的发光信号对于雄性生育力是必需的。
Science. 2020 Jun 5;368(6495):1132-1135. doi: 10.1126/science.aay5134.
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Laminin is the ECM niche for trophoblast stem cells.层粘连蛋白是滋养层干细胞的细胞外基质生态位。
Life Sci Alliance. 2020 Jan 14;3(2). doi: 10.26508/lsa.201900515. Print 2020 Feb.
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Epithelial dynamics in the epididymis: role in the maturation, protection, and storage of spermatozoa.附睾中的上皮动态：在精子成熟、保护和储存中的作用。
Andrology. 2019 Sep;7(5):631-643. doi: 10.1111/andr.12632. Epub 2019 May 1.
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