Premium
The Binding Mode of a Tau Peptide with Tubulin
Author(s) -
Kadavath Harindranath,
Cabrales Fontela Yunior,
Jaremko Mariusz,
Jaremko Łukasz,
Overkamp Kerstin,
Biernat Jacek,
Mandelkow Eckhard,
Zweckstetter Markus
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201712089
Subject(s) - microtubule , tubulin , mutagenesis , phosphorylation , tau protein , biophysics , peptide , binding site , microtubule polymerization , protein–protein interaction , function (biology) , chemistry , binding domain , biology , microbiology and biotechnology , biochemistry , mutation , medicine , disease , pathology , alzheimer's disease , gene
The microtubule‐associated protein Tau promotes the polymerization of tubulin and modulates the function of microtubules. As a consequence of the dynamic nature of the Tau–tubulin interaction, the structural basis of this complex has remained largely elusive. By using NMR methods optimized for ligand–receptor interactions in combination with site‐directed mutagenesis we demonstrate that the flanking domain downstream of the four microtubule‐binding repeats of Tau binds competitively to a site on the α‐tubulin surface. The binding process is complex, involves partial coupling of different interacting regions, and is modulated by phosphorylation at Y394 and S396. This study strengthens the hypothesis of an intimate relationship between Tau phosphorylation and tubulin binding and highlights the power of the INPHARMA NMR method to characterize the interaction of peptides derived from intrinsically disordered proteins with their molecular partners.