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Structural Mechanism of Barriers to Interspecies Seeding Transmissibility of Full-Length Prion Protein Amyloid

文献类型：期刊论文

作者Ma, Tao1,4; Deng, Jing1,4; Ma, Shaojie1,2; Zhao, Weijing1; Chang, Ziwei1; Yu, Kunqian3,4; Yang, Jun1,2
刊名CHEMBIOCHEM
出版日期2019-11-04
卷号20期号:21页码:2757-2766
关键词amyloid fibrils molecular dynamics NMR spectroscopy prions seeding species barriers
ISSN号1439-4227
DOI10.1002/cbic.201900218
通讯作者Yu, Kunqian(yukunqian@simm.ac.cn) ; Yang, Jun(yangjun@wipm.ac.cn)
英文摘要A puzzling feature of prion diseases is the cross-species barriers. The detailed molecular mechanisms underlying these interspecies barriers remain poorly understood because of a lack of high-resolution structural information on the scrapie isoform of the prion protein (PrPSc). In this study we identified the critical role of the residues 165/167 in the barrier to seeding mouse PrP (mPrP) fibril seeds to human cellular prion protein (PrP (c)). Solid-state NMR revealed a C-terminal beta-sheet core spanning residues 165-230 and the packing arrangement of mPrP fibrils. Residues 165/167 are located on one end of the fibril core. Molecular dynamics simulations demonstrated that the stabilities of the seeding-induced beta-strand structures are significantly impacted by hydrogen bonds involving the side chain of residue 167 and steric resistance involving residue 165. These findings suggest that the alpha 2-beta 2 loop containing residues 165/167 could be the initial site of seed-template conformational conversion.
WOS关键词DYNAMICS ; FIBRILS ; DISEASE ; CONVERSION ; SEQUENCE ; PARALLEL ; FORM
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000495124700008
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/281938]  
专题新药研究国家重点实验室
通讯作者Yu, Kunqian; Yang, Jun
作者单位1.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst, Stare Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan 430071, Hubei, Peoples R China
2.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430071, Hubei, Peoples R China
3.Chinese Acad Sci, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai Inst Mat Med,Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Tao,Deng, Jing,Ma, Shaojie,et al. Structural Mechanism of Barriers to Interspecies Seeding Transmissibility of Full-Length Prion Protein Amyloid[J]. CHEMBIOCHEM,2019,20(21):2757-2766.
APA Ma, Tao.,Deng, Jing.,Ma, Shaojie.,Zhao, Weijing.,Chang, Ziwei.,...&Yang, Jun.(2019).Structural Mechanism of Barriers to Interspecies Seeding Transmissibility of Full-Length Prion Protein Amyloid.CHEMBIOCHEM,20(21),2757-2766.
MLA Ma, Tao,et al."Structural Mechanism of Barriers to Interspecies Seeding Transmissibility of Full-Length Prion Protein Amyloid".CHEMBIOCHEM 20.21(2019):2757-2766.

入库方式： OAI收割

来源：上海药物研究所

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