Structural packing of the non-amyloid component core domain in α-synuclein plays a role in the stability of the fibrils

Karina Abramov-Harpaz, Sapir Lan-Mark, Yifat Miller

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson's disease (PD) is one of many neurodegenerative diseases. The protein associated with PD is α-synuclein (AS). Aggregation of AS protein into oligomers, protofilaments, and finally to fibrils yields to the development of PD. The aggregation process of AS leads to the formation of polymorphic AS fibrils. Herein, we compared four polymorphic full-length AS1140 fibrils, using extensive computational tools. The main conclusion of this study emphasizes the role of the structurally packed non-amyloid component (NAC) core domain in AS fibrils. Polymorphic AS fibrils that presented a packed NAC core domain, exhibited more β-sheets and fewer fluctuations in the NAC domain. Hence, these AS fibrils are more stable and populated than the AS fibrils, by which the NAC domains are more exposed, more fluctuate and less packed in the fibrillary structure. Therefore, this study emphasizes the importance of the NAC domain packing in the morphology of AS fibrils. The results obtained in this study will initiate future studies to develop compounds to prevent and inhibit AS aggregation.

Original languageAmerican English
Article number107239
JournalBiophysical Chemistry
Volume310
DOIs
StatePublished - 1 Jul 2024

Keywords

  • Amyloids
  • Neurodegenerative diseases
  • Non-amyloid component
  • Parkinson's disease
  • Protein aggregation
  • Self-assembly

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Organic Chemistry

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