title: Direct Observation of Aggregation-Induced Backbone Conformational Changes in Tau Peptides.
abstract: In tau proteins, the hexapeptides in the R2 and R3 repeats are known to initiate tau fibril formation, which causes a class of neurodegenerative diseases called the taupathies. We show that in R3, in addition to the presence of the hexapeptides, the correct turn conformation upstream to it is also essential for producing prion-like fibrils that are capable of propagation. A time-dependent NMR aggregation assay of a slow fibril forming R3-S316P peptide revealed a trans to cis equilibrium shift in the peptide-bond conformation preceding P316 during the growth phase of the aggregation process. S316 was identified as the key residue in the turn that confers templating capacity on R3 fibrils to accelerate the aggregation of the R3-S316P peptide. These results on the specific interactions and conformational changes responsible for tau aggregation could prove useful for developing an efficient therapeutic intervention in Alzheimer's disease.
authors: School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER-TVM), CET campus, Trivandrum-, 695016, India.
authors: A C
authors: AC
authors: Jiji
authors: School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER-TVM), CET campus, Trivandrum-, 695016, India.
authors: A
authors: A
authors: Shine
authors: School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER-TVM), CET campus, Trivandrum-, 695016, India. vinesh@iisertvm.ac.in.
authors: Vinesh
authors: V
authors: Vijayan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D066329:Protein Aggregates; D016875:tau Proteins
keywords: Alzheimer's disease; NMR spectroscopy; cis-trans isomerism; fibrillation; peptides