Residue-based propensity of aggregation in the Tau amyloidogenic hexapeptides AcPHF6*and AcPHF6
| Title | Residue-based propensity of aggregation in the Tau amyloidogenic hexapeptides AcPHF6*and AcPHF6 |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Dangi, A, Balmik, AAnkur, Ghorpade, AKisan, Gorantla, NVijay, Sonawane, SKishor, Chinnathambi, S, Marelli, UKiran |
| Journal | RSC Advances |
| Volume | 10 |
| Issue | 46 |
| Pagination | 27331-27335 |
| Date Published | JUL |
| Type of Article | Article |
| Abstract | In Alzheimer's disease and related tauopathies, the aggregation of microtubule-associated protein, Tau, into fibrils occursviathe interaction of two hexapeptide motifs PHF*(275)VQIINK(280)and PHF(306)VQIVYK(311)as beta-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. |
| DOI | 10.1039/d0ra03809a |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 3.119 |