Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus

Conopeptides from the marine cone snails are a mixture of cysteine-rich active peptides, representing a unique and fertile resource for neuroscience research and drug discovery. The ConoServer database includes 8,134 conopeptides from 122 Conus species, yet many more natural conopeptides remain to b...

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Autores principales:	Han Zhang, Lei Wang, Xiang Yang, Zhiwei Lian, Yinbin Qiu, Zhanying Dong, Xuedong Wu, Xinghua Pan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	diversity conopeptides de novo sequencing LC-MS/MS pethidine hydrochloride Science Q General. Including nature conservation, geographical distribution QH1-199.5
Acceso en línea:	https://doaj.org/article/55a25c4e22d8478f980d0d2fc7d8dde1
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spelling	oai:doaj.org-article:55a25c4e22d8478f980d0d2fc7d8dde12021-11-12T04:38:03ZIdentification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus2296-774510.3389/fmars.2021.766792https://doaj.org/article/55a25c4e22d8478f980d0d2fc7d8dde12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmars.2021.766792/fullhttps://doaj.org/toc/2296-7745Conopeptides from the marine cone snails are a mixture of cysteine-rich active peptides, representing a unique and fertile resource for neuroscience research and drug discovery. The ConoServer database includes 8,134 conopeptides from 122 Conus species, yet many more natural conopeptides remain to be discovered. Here, we identified 517 distinct conopeptide precursors in Conus quercinus using de novo deep transcriptome sequencing. Ten of these precursors were verified at the protein level using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The combined gene and protein analyses revealed two novel gene superfamilies (Que-MNCLQ and Que-MAMNV), and three other gene superfamilies (N, P, and I1) were reported for the first time in C. quercinus. From the Que-MAMNV superfamily, a novel conotoxin, Que-0.1, was obtained via cloning and prokaryotic expression. We also documented a new purification process that can be used to induce the expression of conopeptides containing multiple pairs of disulfide bonds. The animal experiments showed that Que-0.1 strongly inhibited neuroconduction; the effects of Que-1.0 were 6.25 times stronger than those of pethidine hydrochloride. In addition, a new cysteine framework (CC-C-C-C-C-C-CC-C-C-C-C-C) was found in C. quercinus. These discoveries accelerate our understanding of conopeptide diversity in the genus, Conus and supply promising materials for medical research.Han ZhangHan ZhangHan ZhangLei WangXiang YangXiang YangXiang YangZhiwei LianZhiwei LianYinbin QiuYinbin QiuZhanying DongZhanying DongXuedong WuXuedong WuXinghua PanXinghua PanXinghua PanXinghua PanFrontiers Media S.A.articlediversityconopeptidesde novo sequencingLC-MS/MSpethidine hydrochlorideScienceQGeneral. Including nature conservation, geographical distributionQH1-199.5ENFrontiers in Marine Science, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diversity conopeptides de novo sequencing LC-MS/MS pethidine hydrochloride Science Q General. Including nature conservation, geographical distribution QH1-199.5
spellingShingle	diversity conopeptides de novo sequencing LC-MS/MS pethidine hydrochloride Science Q General. Including nature conservation, geographical distribution QH1-199.5 Han Zhang Han Zhang Han Zhang Lei Wang Xiang Yang Xiang Yang Xiang Yang Zhiwei Lian Zhiwei Lian Yinbin Qiu Yinbin Qiu Zhanying Dong Zhanying Dong Xuedong Wu Xuedong Wu Xinghua Pan Xinghua Pan Xinghua Pan Xinghua Pan Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
description	Conopeptides from the marine cone snails are a mixture of cysteine-rich active peptides, representing a unique and fertile resource for neuroscience research and drug discovery. The ConoServer database includes 8,134 conopeptides from 122 Conus species, yet many more natural conopeptides remain to be discovered. Here, we identified 517 distinct conopeptide precursors in Conus quercinus using de novo deep transcriptome sequencing. Ten of these precursors were verified at the protein level using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The combined gene and protein analyses revealed two novel gene superfamilies (Que-MNCLQ and Que-MAMNV), and three other gene superfamilies (N, P, and I1) were reported for the first time in C. quercinus. From the Que-MAMNV superfamily, a novel conotoxin, Que-0.1, was obtained via cloning and prokaryotic expression. We also documented a new purification process that can be used to induce the expression of conopeptides containing multiple pairs of disulfide bonds. The animal experiments showed that Que-0.1 strongly inhibited neuroconduction; the effects of Que-1.0 were 6.25 times stronger than those of pethidine hydrochloride. In addition, a new cysteine framework (CC-C-C-C-C-C-CC-C-C-C-C-C) was found in C. quercinus. These discoveries accelerate our understanding of conopeptide diversity in the genus, Conus and supply promising materials for medical research.
format	article
author	Han Zhang Han Zhang Han Zhang Lei Wang Xiang Yang Xiang Yang Xiang Yang Zhiwei Lian Zhiwei Lian Yinbin Qiu Yinbin Qiu Zhanying Dong Zhanying Dong Xuedong Wu Xuedong Wu Xinghua Pan Xinghua Pan Xinghua Pan Xinghua Pan
author_facet	Han Zhang Han Zhang Han Zhang Lei Wang Xiang Yang Xiang Yang Xiang Yang Zhiwei Lian Zhiwei Lian Yinbin Qiu Yinbin Qiu Zhanying Dong Zhanying Dong Xuedong Wu Xuedong Wu Xinghua Pan Xinghua Pan Xinghua Pan Xinghua Pan
author_sort	Han Zhang
title	Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
title_short	Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
title_full	Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
title_fullStr	Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
title_full_unstemmed	Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
title_sort	identification of novel conopeptides and distinct gene superfamilies in the marine cone snail conus quercinus
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/55a25c4e22d8478f980d0d2fc7d8dde1
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Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus

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