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Zn 2+ Interrupts R4‐R3 Association Leading to Accelerated Aggregation of Tau Protein
Author(s) -
Jiji A. C.,
Arshad A.,
Dhanya S. R.,
Shabana P. S.,
Mehjubin C. K.,
Vijayan Vinesh
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704555
Subject(s) - chemistry , peptide , biophysics , cysteine , amino acid , tau protein , divalent , protein aggregation , biochemistry , biology , enzyme , medicine , disease , organic chemistry , alzheimer's disease , pathology
Direct binding of divalent metal ion, especially Zn 2+ , have been shown to increase the rate of tau aggregation and enhance tau toxicity in cells. Hence, understanding the molecular basis of the Zn 2+ ‐accelerated tau aggregation can potentially determine the molecular interactions modulating tau aggregation. Herein, we show that Zn 2+ coordinates through the cysteine in R3 repeat and significantly accelerates the aggregation rate of the three repeat tau constructs (K19) but that the coordination is incapable of increasing the aggregation rate of the 20 amino acid peptide derived from the R3 repeat (R3) of tau. The NMR characterization of the binding of Zn 2+ to K19, together with the aggregation studies with K19, R3 and R4 peptides, reveal the presence of an aggregation‐inhibitory interaction between the R3 and R4 repeat of K19. Our data show that binding of Zn 2+ to R3 repeat of tau, weaken the aggregation‐inhibiting influence between R3 and R4 repeats, leading to faster aggregation of tau protein.