Biophysical characterization of oligomerization and fibrillization of the G131V pathogenic mutant of human prion protein

查看全文 作　　者：Meilan [1]Zhang;Haoran [1]Zhang;Hongwei [1]Yao;Chenyun [1]Guo;Donghai [1]Lin

机构地区：[1]MOE Key Laboratory of Spectrochemical Analysis and Instrumentation,Key Laboratory of Chemical Biology of Fujian Province,College of Chemistry and Chemical Engineering,Xiamen University,Xiamen 361005,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2019年第51卷第12期,共10页

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.31670741 and 81661138005);the National Key Research and Development Project of China(No.2016YFA0500600). 摘　　要：The pathogenesis of fatal neurodegenerative prion diseases is closely associated with the conversion of a-helix-rich cellular prion protein into p-sheet-rich scrapie form.Pathogenic point mutations of prion proteins usually promote the conformational conversion and trigger inherited prion diseases.The G131V mutation of human prion protein(HuPrP)was identified to be involved in Gerstmann-Straussler-Scheinker syndrome.Few studies have been carried out to address the pathogenesis of the G131V mutant.Here,we addressed the effects of the G131V mutation on oligomerization and fibrillization of the full-length HuPrP(23-231)and truncated HuPrP(91-231)proteins.The G131V mutation promotes the oligomerization but alleviates the fibrillization of HuPrE implying that the oligomerization might play a crucial role in the pathogenic mechanisms of the G131V mutant.Moreover,the flexible N-terminal fragment in either the wild-type or the G131V mutant HuPrP in creases the oligomerizati on tenden cies but decreases the fibrillizati on tendencies.Furthermore,this mutation significantly alters the tertiary structure of human PrPc and might distinctly ch a nge the conformati onal conversion tendency.Interestingly,both gua ni?dine hydrochloride denaturation and thermal denaturation experiments showed that the G131V mutation does not sign ificantly ch a nge the thermodynamic stabilities of the HuPrP protei ns.This work may be of ben efit to a mecha nistic un derstandi ng of the conformational con version of prion proteins and also provide clues for the prevention and treatment of prion diseases. 关键词：human PRION protein G131V MUTANT OLIGOMERIZATION FIBRILLIZATION THERMODYNAMIC stability

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Biophysical characterization of oligomerization and fibrillization of the G131V pathogenic mutant of human prion protein

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