Cross-linking and amyloid formation by N- and C-terminal cysteine derivatives of human apolipoprotein C-II

Abstract

We have investigated the effect of disulfide cross-linking on amyloid formation by human apolipoprotein (apo) C-II. Three derivatives of apoC-II were generated by inserting a cysteine residue on either the N-terminus (CN-apoC-II), C-terminus (CC-apoC-II), or both termini (CNCc-apoC-II). Under reducing conditions, all derivatives formed amyloid with a fibrous ribbon morphology similar to that of wild-type apoC-II. Under oxidizing conditions, CN- and CNCC-apoC-II formed a highly tangled network of fibrils, suggesting that the addition of an N-terminal cysteine to apoC-II promotes interfibril disulfide cross-links. Fibrils formed by CC-apoC-II under oxidizing conditions were closely packed but ..