Oligomer Formation of Toxic and Functional Amyloid Peptides Studied with Atomistic Simulations.

Abstract

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.

• Authors: Martín Carballo-Pacheco, Ahmed E Ismail, Birgit Strodel
• Journal: The journal of physical chemistry. B (J Phys Chem B) Vol. 119 Issue 30 Pg. 9696-705 (Jul 30 2015) ISSN: 1520-5207 [Electronic] United States
• PMID: 26130191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Kassinin
• Neurokinin B

Topics

• Amino Acid Sequence
• Amyloid beta-Peptides (chemistry)
• Kassinin (chemistry)
• Molecular Dynamics Simulation
• Molecular Sequence Data
• Neurokinin B (chemistry)
• Protein Multimerization
• Protein Structure, Secondary