title: Tau binds ATP and induces its aggregation.
abstract: Tau is a microtubule-associated protein mainly found in neurons. The protein is associated with process of microtubule assembly, which plays an important role in intracellular transport and cell structure of the neuron. Tauopathies are a group of neurodegenerative diseases specifically associated with tau abnormalities. While a well-defined mechanism remains unknown, most facts point to tau as a prominent culprit in neurodegeneration. In most cases of Tauopathies, aggregates of hyperphosphorylated tau have been found. Two proposals are present when discussing tau toxicity, one being the aggregation of tau proteins and the other points toward a conformational change within the protein. Previous work we carried out showed tau hyperphosphorylation promotes tau to behave abnormally resulting in microtubule assembly disruption as well as a breakdown in tau self-assembly. We found that tau's N-terminal region has a putative site for ATP/GTP binding. In this paper we demonstrate that tau is able to bind ATP and not GTP, that this binding induces tau self-assembly into filaments. At 1 mM ATP the filaments are 4-7 nm in width, whereas at 10 mM ATP the filaments appeared to establish lateral interaction, bundling and twisting, forming filaments that resembled the Paired Helical Filaments (PHF) isolated from Alzheimer disease brain. ATP-induced self-assembly is not energy dependent because the nonhydrolysable analogue of the ATP induces the same assembly.
authors.affiliation: Department of Biology and Center for Developmental Neuroscience, College of Staten Island and Graduate Center, The City University of New York, Staten Island, New York, 10314.
authors.forename: Mina
authors.initials: M
authors.lastname: Farid
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Corbo
authors.forename: Alejandra Del C
authors.initials: Adel C
authors.lastname: Alonso
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011489:Protein Denaturation; D055503:Protein Multimerization; D024801:Tauopathies / Q000473:pathology / Q000503:physiopathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D000255:Adenosine Triphosphate
keywords: ATP; filaments; self-assembly; tau