Residue-based Propensity of Aggregation in the Tau Amyloidogenic Hexapeptides AcPHF6* and AcPHF6

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 May 6

PMID 35516938

Authors

Abha Dangi

Abhishek Ankur Balmik

Archana Kisan Ghorpade

Nalini Vijay Gorantla

Shweta Kishor Sonawane

Subashchandrabose Chinnathambi

Udaya Kiran Marelli

Affiliations

Soon will be listed here.

Abstract

In Alzheimer's disease and related tauopathies, the aggregation of microtubule-associated protein, Tau, into fibrils occurs the interaction of two hexapeptide motifs PHF* VQIINK and PHF VQIVYK 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.

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