TY  - JOUR
AU  - Carballo-Pacheco, Martín
AU  - Ismail, Ahmed E.
AU  - Strodel, Birgit
TI  - Oligomer Formation of Toxic and Functional Amyloid Peptides Studied with Atomistic Simulations
JO  - The journal of physical chemistry  / B
VL  - 119
IS  - 30
SN  - 1520-5207
CY  - Washington, DC
PB  - Soc.
M1  - FZJ-2015-07321
SP  - 9696 - 9705
PY  - 2015
AB  - Amyloids are associated with diseases, including Alzheimer’s, as well as functional roles such as storage of peptide hormones. It is still unclear what differences exist between aberrant and functional amyloids. However, it is known that soluble oligomers formed during amyloid aggregation are more toxic than the final fibrils. Here, we perform molecular dynamics simulations to study the aggregation of the amyloid-β peptide Aβ25–35, associated with Alzheimer’s disease, and two functional amyloid-forming tachykinin peptides: kassinin and neuromedin K. Although the three peptides have similar primary sequences, tachykinin peptides, in contrast to Aβ25–35, form nontoxic amyloids. Our simulations reveal that the charge of the C-terminus is essential to controlling the aggregation process. In particular, when the kassinin C-terminus is not amidated, the aggregation kinetics decreases considerably. In addition, we observe that the monomeric peptides in extended conformations aggregate faster than those in collapsed hairpin-like conformations.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000359031400022
C6  - pmid:26130191
DO  - DOI:10.1021/acs.jpcb.5b04822
UR  - https://juser.fz-juelich.de/record/279306
ER  -