Journal article

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..

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