Tau Structures

Abstract

Tau is a microtubule-associated protein that plays an important role in axonal stabilization, neuronal development, and neuronal polarity. In this review, we focus on the primary, secondary, tertiary, and quaternary tau structures. We describe the structure of tau from its specific residues until its conformation in dimers, oligomers, and larger polymers in physiological and pathological situations.

Keywords: PHFs; aggregation; microtubule-associated proteins; motifs; posttranslational modifications; tau residues; tubuling binding.

Figure 1

Tau residues and tau regions. (A) The localization in tau molecules of some tau residues is shown. (B) The different tau regions, including the microtubule binding repeats are shown. (C) Intramolecular interactions, like that described for “paper-clip” structure (see text and reference, Jeganathan et al., 2006) could prevent the tau self-interaction by masking the region(s) involved in that interaction.

Figure 2

Interaction tau-tau. Tau protein could be found as an extended common long protein that could bind to other proteins, including itself, in this extended fashion (Hirokawa et al., 1988). The Figure shows how two tau molecules could interact, in an antiparallel fashion, through their microtubule-binding domain where cysteine residues are present.

Figure 3

Hypothetical tau circular-like structure. (A) Tau granule (circular-like) structures have been previously reported (Rábano et al., ; Takashima, 2013). In the Figure, it is shown an hypothetical closed structure playing with parallel and antiparallel tau molecules. In that structure, a hole in the center surrounded by C-terminal sequences of tau molecule can be found. Since tau C-terminal sequences contain several acidic residues, it is possible the reaction of those residues with metals. It may take place in argylophylic grains. (B) A 3D-like image of the structure is shown. In that image parallel and antiparallel forms, with the C-terminal (blue) or N-terminal (violet), regions of tau molecule at the surface, could be present. It is proposed that those having the C-terminal inside the structure could react with cations.