Residue-based propensity of aggregation in the Tau amyloidogenic hexapeptides AcPHF6* and AcPHF6
Abha Dangi, Abhishek Ankur Balmik, Archana Kisan Ghorpade, Nalini Vijay Gorantla, Shweta Kishor Sonawane, Subashchandrabose Chinnathambi, Udaya Kiran Marelli
Abstract
as β-sheets. To understand the role of the constituent amino acids of PHF and PHF* in the aggregation, a set of 12 alanine mutant peptides was synthesized by replacing each amino acid in PHF and PHF* with alanine and they were characterized by nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), transmission electron microscopy (TEM) and ThS/ANS fluorescence assay. Our studies show that while the aggregation was suppressed in most of the alanine mutant peptides, replacement of glutamine by alanine in both PHF and PHF* enhanced the fibrillization.
Topics & Concepts
AlanineChemistryResidue (chemistry)GlutamineStereochemistryBiochemistryBiophysicsAmino acidBiologyAlzheimer's disease research and treatmentsProtein Structure and DynamicsEnzyme Structure and Function