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Solution NMR Studies of Recombinant Aβ(1–42): From the Presence of a Micellar Entity to Residual β‐Sheet Structure in the Soluble Species
Author(s) -
Wälti Marielle Aulikki,
Orts Julien,
Vögeli Beat,
Campioni Silvia,
Riek Roland
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402595
Subject(s) - micelle , chemistry , fibril , biophysics , kinetics , random coil , amyloid fibril , peptide , crystallography , aqueous solution , biochemistry , protein secondary structure , organic chemistry , amyloid β , biology , medicine , pathology , quantum mechanics , physics , disease
Amyloid‐β (Aβ) peptide is the major component found in senile plaques of Alzheimer's disease patients. The 42‐residue fragment Aβ(1–42) is proposed to be one of the most pathogenic species therein. Here, the soluble Aβ(1–42) species were analyzed by various liquid‐state NMR methods. Transient formation of a micelle species was observed at the onset of the aggregation kinetics. This micelle is dissolved after approximately one day. Subsequent loss of this species and the formation of protofibrils are proposed to be the route of fibril formation. Consequently, the observed micelle species is suggested to be on an off‐pathway mechanism. Furthermore, characterization of the NMR‐observable soluble species shows that it is a random‐coil‐like entity with low propensities for four β‐strands. These β‐strands correlate with the β‐strand segments observed in Aβ fibrils. This finding indicates that the 3D structure of the fibrils might already be predisposed in the soluble species.