Differential copper binding to alpha-synuclein and its disease-associated mutants affect the aggregation and amyloid formation

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• 作者：Priyatosh Ranjan^a ; ¹ ; Dhiman Ghosh^a ; ¹ ; Deepthi S. Yarramala^b ; Subhadeep Das^a ; ^c ; Samir K. Maji^a ; Ashutosh Kumar^a ; ^{ashutoshk@iitb.ac.in}
• 关键词：α-Syn H50Q ; α-Syn G51D ; Non-amyloid-β component ; Copper ; Long-range contacts
• 刊名：Biochimica et Biophysica Acta (BBA) - General Subjects
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：1861
• 期：2
• 页码：365-374
• 全文大小：2254 K
• 卷排序：1861

文摘

Residue specific mapping of Cu2 + binding sites along with the strength and order of binding was studied in the wild type α-Syn and recently discovered familial mutants i.e. H50Q and G51D. The region 48-53 of H50Q does not bind to Cu2 +, unlike wild-type and G51D. Even though the binding of Cu2 + was less in H50Q, the rate of fibril formation was higher compared to the wild-type. The aggregation kinetics of the slower aggregating familial mutant G51D showed a significant decrease in the lag phase in the presence of Cu2 +. The H50Q fibrillar species were more toxic compared to the fibrillar species generated in the presence of Cu2 +, unlike wild-type.