Charge and Charge-Pair Mutations Alter the Rate of Assembly and Structural Properties of Apolipoprotein C-II Amyloid Fibrils
Yu Mao, Chai Lean Teoh, Shuo Yang, Courtney O Zlatic, Zachary K Rosenes, Paul R Gooley, Geoffrey J Howlett, Michael DW Griffin
Biochemistry | AMER CHEMICAL SOC | Published : 2015
The misfolding, aggregation, and accumulation of proteins as amyloid fibrils is a defining characteristic of several debilitating diseases. Human apolipoprotein C-II (apoC-II) amyloid fibrils are representative of the fibrils formed by a number of plasma apolipoproteins implicated in amyloid-related disease. Previous structural analyses identified a buried charge pair between residues K30 and D69 within apoC-II amyloid fibrils. We have investigated the effects of amino acid substitutions of these residues on apoC-II fibril formation. Two point mutations of apoC-II, D69K and K30D, as well as a reversed ion-pair mutant containing both mutations (KDDK) were generated. Fibril formation by the do..View full abstract
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Awarded by Australian Research Council
Awarded by Australian Research Council Future Fellowship
This work was supported by the Australian Research Council (Projects DP0877800 and DP110103528). M.D.W.G. is the recipient of the C. R. Roper Fellowship and an Australian Research Council Future Fellowship (Project FT140100544).