title: Structural evaluations of tau protein conformation: methodologies and approaches.
abstract: Protein-misfolding diseases are based on a common principle of aggregation initiated by intra- and inter-molecular contacts. The structural and conformational changes induced by biochemical transformations such as post-translational modifications (PTMs), often lead to protein unfolding and misfolding. Thus, these order-to-disorder or disorder-to-order transitions may regulate cellular function. Tau, a neuronal protein, regulates microtubule (MT) structure and overall cellular integrity. However, misfolded tau modified by PTMs results in MT destabilization, toxic tau aggregate formation, and ultimately cell death, leading to neurodegeneration. Currently, the lack of structural information surrounding tau severely limits understanding of neurodegeneration. This minireview focuses on the current methodologies and approaches aimed at probing tau conformation and the role of conformation in various aspects of tau biochemistry. The recent applications of nuclear magnetic resonance, mass spectrometry, Förster resonance electron transfer, and molecular dynamics simulations toward structural analysis of conformational landscapes of tau will be described. The strategies developed for structural evaluation of tau may significantly improve our understanding of misfolding diseases.
authors.affiliation: Department of Chemistry, Oakland University, Rochester, MI 48309, USA.|Department of Chemistry, Oakland University, Rochester, MI 48309, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Zabik
authors.affiliation: Department of Chemistry, Oakland University, Rochester, MI 48309, USA.|Department of Chemistry, Oakland University, Rochester, MI 48309, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Imhof
authors.affiliation: Department of Chemistry, Oakland University, Rochester, MI 48309, USA.|Department of Chemistry, Oakland University, Rochester, MI 48309, USA.
authors.forename: Sanela
authors.initials: S
authors.lastname: Martic-Milne
mesh_terms: D000818:Animals; D006801:Humans; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: FRET; MS; NMR; RMN; SP; dynamique moléculaire; hyper-phosphorylation; hyperphosphorylation; intrinsically disordered proteins; molecular dynamics; protéine tau; protéines intrinsèquement désordonnées; tau protein