A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from D-Conotoxin GeXXA

doi:10.3390/md15060164

	A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from D-Conotoxin GeXXA
	Yang, Longjin 1; Tae, Han-Shen 2; Fan, Zhou3,4 ; Shao, Xiaoxia 1; Xu, Shaoqiong 1; Zhao, Suwen3,4 ; Adams, David J.2; Wang, Chunguang 1
	2017-06
发表期刊	MARINE DRUGS
ISSN	1660-3397
卷号	15 期号:6
发表状态	已发表
DOI	10.3390/md15060164
摘要	Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric D-conotoxin GeXXA was identified to inhibit nAChRs by binding at the top surface of the receptors, and the monomeric C-terminal domain (CTD) of D-GeXXA retains some inhibitory activity. In this study, the internal dimeric N-terminal domain (NTD) of this conopeptide was further investigated. We first developed a regio-selective protection strategy to chemically prepare the anti-parallel dimeric NTD, and found that the isolated NTD part of GeXXA possesses the nAChR-inhibitory activity, the subtype-dependence of which implies a preferred binding of NTD to the subunits of nAChR. Deletion of the NTD N-terminal residues did not affect the activity of NTD, indicating that the N-terminus is not involved in the interaction with nAChRs. By optimizing the sequence of NTD, we obtained a fully active single-chain cyclic NTD, based on which 4 Arg residues were found to interact with nAChRs. These results demonstrate that the NTD part of D-GeXXA is a lid-covering nAChR inhibitor, displaying a novel inhibitory mechanism distinct from other allosteric ligands of nAChRs.
关键词	nAChR conotoxin D-GeXXA NTD lid-covering
收录类别	SCI
语种	英语
资助项目	Australian Research Council (ARC)[DP150103990]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000404526900019
出版者	MDPI AG
WOS关键词	BINDING-SITES ; THERAPEUTICS ; ANTAGONISTS ; HOMOLOG ; DOMAIN ; PAIN
原始文献类型	Article
通讯作者	Adams, David J. ; Wang, Chunguang
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2918
专题	生命科学与技术学院 iHuman研究所_PI研究组_赵素文组生命科学与技术学院_硕士生
通讯作者	Adams, David J.; Wang, Chunguang
作者单位	1.Tongji Univ, Sch Life Sci & Technol, Shanghai Peoples Hosp 10, Dept Cent Lab, Shanghai 200092, Peoples R China 2.Univ Wollongong, IHMRI, Wollongong, NSW 2522, Australia 3.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201219, Peoples R China
推荐引用方式 GB/T 7714	Yang, Longjin,Tae, Han-Shen,Fan, Zhou,et al. A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from D-Conotoxin GeXXA[J]. MARINE DRUGS,2017,15(6).
APA	Yang, Longjin.,Tae, Han-Shen.,Fan, Zhou.,Shao, Xiaoxia.,Xu, Shaoqiong.,...&Wang, Chunguang.(2017).A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from D-Conotoxin GeXXA.MARINE DRUGS,15(6).
MLA	Yang, Longjin,et al."A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from D-Conotoxin GeXXA".MARINE DRUGS 15.6(2017).