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

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* (275)VQIINK(280) and PHF (306)VQIVYK(311) as β-sheets. To understand the role of the constituent amino acids of PHF and...

Descripción completa

Detalles Bibliográficos
Autores principales: Dangi, Abha, Balmik, Abhishek Ankur, Ghorpade, Archana Kisan, Gorantla, Nalini Vijay, Sonawane, Shweta Kishor, Chinnathambi, Subashchandrabose, Marelli, Udaya Kiran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055513/
https://www.ncbi.nlm.nih.gov/pubmed/35516938
http://dx.doi.org/10.1039/d0ra03809a
Descripción
Sumario: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* (275)VQIINK(280) and PHF (306)VQIVYK(311) 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.

Ejemplares similares