AMYLOID-DETERMINING RESIDUES IN MOUSE SERUM AMYLOID A

摘要

Mouse SAA1.1 (formerly SAA2) and SAA2.2 (formerly SAA CE/J) differ at only six of 103 positions (positions 6, 7, 11, 60, 63, and 101) (1, 2). SAA1.1 is highly amyloidogenic in mice and in macrophage and fibroblast cultures. In contrast, SAA2.2 does not form amyloid (3). Previous findings have indicated lack of SAA2.2 amyloidogenecity is dictated primarily by its structure (4). Three of the six differences between SAA2.2 and SAA1.1 are located in the N-terminal region. In vitro fibril formation has been achieved from peptides corresponding to the N-terminal portion of SAA1.1 (5), whereas recombinant truncated SAA lacking the first eleven residues fails to undergo in vitro fibril formation (6). Thus, this region is regarded as a determinant of fibrillogenesis. The aim of our study was to determine the amyloid-forming capability of various mutants of SAA1.1 and SAA2.2 in cell culture systems and thereby identify specific residues in SAA1.1 that correlate not only with fibrillogenesis but also with production of stable amyloid deposits.