Issue 46, 2020
From the journal:

RSC Advances

Residue-based propensity of aggregation in the Tau amyloidogenic hexapeptides AcPHF6* and AcPHF6†

Abha Dangi,‡abc   Abhishek Ankur Balmik,‡cd   Archana Kisan Ghorpade,ab   Nalini Vijay Gorantla,cd   Shweta Kishor Sonawane,cd   Subashchandrabose Chinnathambi ORCID logo *cd  and  Udaya Kiran Marelli ORCID logo *abc  

* Corresponding authors

a Central NMR Facility, CSIR-National Chemical Laboratory, Dr HomiBhabha Road, 411008 Pune, India

b Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr HomiBhabha Road, 411008 Pune, India

c Academy of Scientific and Innovative Research (AcSIR), 110025 New Delhi, India

d Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Dr HomiBhabha Road, 411008 Pune, India

Abstract

In Alzheimer's disease and related tauopathies, the aggregation of microtubule-associated protein, Tau, into fibrils occurs via the interaction of two hexapeptide motifs PHF* 275VQIINK280 and PHF 306VQIVYK311 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.

Graphical abstract: Residue-based propensity of aggregation in the Tau amyloidogenic hexapeptides AcPHF6* and AcPHF6

About
Cited by
Related
Download options Please wait...

Associated articles

Supplementary files

Article information

DOI
https://doi.org/10.1039/D0RA03809A
Article type
Paper
Submitted
28 Apr 2020
Accepted
09 Jul 2020
First published
21 Jul 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 27331-27335

Permissions

Request permissions

Residue-based propensity of aggregation in the Tau amyloidogenic hexapeptides AcPHF6* and AcPHF6

A. Dangi, A. A. Balmik, A. K. Ghorpade, N. V. Gorantla, S. K. Sonawane, S. Chinnathambi and U. K. Marelli, RSC Adv., 2020, 10, 27331 DOI: 10.1039/D0RA03809A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements