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Importance of micelle‐like multimers in the atypical aggregation kinetics of N‐terminal serum amyloid A peptides
Author(s) -
Ahmed Ikhlaus,
Jones Eric M.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13334
Subject(s) - chemistry , kinetics , peptide , micelle , amyloid (mycology) , biophysics , amyloid fibril , fibril , amyloid disease , serum amyloid a , biochemistry , amyloid β , aqueous solution , inflammation , biology , organic chemistry , medicine , inorganic chemistry , physics , disease , quantum mechanics , immunology
Amyloid formation occurs via numerous complex mechanisms, often involving intermediates. This study examines the mechanism of amyloidogenesis in two N‐terminal fragments of serum amyloid A ( SAA ), which are known to exhibit dramatically different amyloid structures. Fibrillization kinetics by these peptides are found to exhibit two unusual features: slower rates at higher peptide concentration, and complete insensitivity to addition of pre‐formed seed. Additionally, we find that these peptides form micelle‐like oligomers in solution. Our results imply an unusual dual role of micellar oligomers in amyloidogenesis, in which these particles act both as an off‐pathway reservoir of peptide, and an inhibitory aggregate that slows amyloid growth. We anticipate that this mechanism of fibril formation may exist in other hydrophobic amyloid‐forming peptides and proteins.