Conformational Compatibility Is Essential for Heterologous Aggregation of α-Synuclein

A. Sidhu, Gezina M.J. Segers-Nolten, Vinod Subramaniam

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

Under aggregation-prone conditions, soluble amyloidogenic protein monomers can self-assemble into fibrils or they can fibrillize on preformed fibrillar seeds (seeded aggregation). Seeded aggregations are known to propagate the morphology of the seeds in the event of cross-seeding. However, not all proteins are known to cross-seed aggregation. Cross-seeding has been proposed to be restricted either because of differences in the protein sequences or because of conformations between the seeds and the soluble monomers. Here, we examine cross-seeding efficiency between three α-synuclein sequences, wild-type, A30P, and A53T, each varying in only one or two amino acids but forming morphologically distinct fibrils. Results from bulk Thioflavin-T measurements, monomer incorporation quantification, single fibril fluorescence microscopy, and atomic force microscopy show that under the given solution conditions conformity between the conformation of seeds and monomers is essential for seed elongation. Moreover, elongation characteristics of the seeds are defined by the type of seed.
Original languageEnglish
Pages (from-to)719-727
JournalACS chemical neuroscience
Volume7
Issue number6
DOIs
Publication statusPublished - 2016

Keywords

  • METIS-317777
  • IR-101197

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