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	Prion dimer is heterogenous and is modulated by multiple negative and positive motifs
	Gao, Zhenxing1,2; Shi, Jing3; Cai, Lili1; Luo, Minhua1; Wong, Boon-Seng4; Dong, Xiaoping5; Sy, Man-Sun6; Li, Chaoyang1,2
刊名	Biochemical and biophysical research communications
	2019-02-05
卷号	509期号:2页码:570-576
关键词	Prion protein Disulfide bond Fatal familial insomnia Prp dimer Prp aggregation
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2018.12.113
通讯作者	Li, chaoyang(cyli@wh.iov.cn)
英文摘要	The conversion of the normal prion protein (prp) into a scrapie priori (prpsc) is incompletely understood. theoretically, the smallest prp aggregate is a dimer. human prp contains two cysteines at positions 179 (c179) and 214 (c214) enabling disulfide bonding. here, we report that our recombinant human prp (r-hprp) preparations contain 0.2-0.8% dimer, which is linked by either one or two disulfide bonds, connected by c179-c179, c214-c214, or c179-c214. furthermore, dimerization is regulated by multiple motifs. while residues 36-42 inhibit, residues 90-125, and 195-212 promote dimerization. mutating individual residue between 36 and 42 enhances dimerization whereas mutating the positively charged residues within 95-115, or the negatively charged residues within 195-212 prevent dimerization. although deletion of the entire octapeptide-repeat (5or) region prevents dimerization, mutating the histidines within the 5or enhances dimerization. in addition, we found that two out of three brain lysates from patients with inherited prion disease had more prp dimers than controls. thus, prp dimerlzation may contribute to prion diseases. (c) 2018 elsevier inc. all rights reserved.
WOS关键词	CONFORMATIONAL-CHANGES ; PROTEASE RESISTANCE ; PRP ; AGGREGATION ; RECOMBINANT ; CONVERSION ; MECHANISM ; PROTEINS ; BINDING ; DOMAIN
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000458094800037
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373190
专题	武汉病毒研究所
通讯作者	Li, Chaoyang
作者单位	1.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, Hubei, Peoples R China 2.Guangzhou Med Univ, Affiliated Canc Hosp & Inst, 78 Heng Zhi Gang Rd, Guangzhou 510095, Guangdong, Peoples R China 3.Xiangyang Ctr Dis Control & Prevent, 172 Tan Xi Rd, Xiangyang, Hubei, Peoples R China 4.Singapore Inst Technol, Hlth & Social Sci Cluster, Singapore, Singapore 5.Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Infect Dis Prevent & Control, Natl Inst Viral Dis Control & Prevent,Chinese Ctr, Chang Bai Rd 155, Beijing 102206, Peoples R China 6.Case Western Reserve Univ, Sch Med, Dept Pathol, 2103 Cornell Rd, Cleveland, OH 44106 USA
推荐引用方式 GB/T 7714	Gao, Zhenxing,Shi, Jing,Cai, Lili,et al. Prion dimer is heterogenous and is modulated by multiple negative and positive motifs[J]. Biochemical and biophysical research communications,2019,509(2):570-576.
APA	Gao, Zhenxing.,Shi, Jing.,Cai, Lili.,Luo, Minhua.,Wong, Boon-Seng.,...&Li, Chaoyang.(2019).Prion dimer is heterogenous and is modulated by multiple negative and positive motifs.Biochemical and biophysical research communications,509(2),570-576.
MLA	Gao, Zhenxing,et al."Prion dimer is heterogenous and is modulated by multiple negative and positive motifs".Biochemical and biophysical research communications 509.2(2019):570-576.

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