Figure 1. Five functional domains of tubulin.

Tubulin is comprised of three separate functional domains that participate in heterodimer stability, longitudinal and lateral protofilament interactions, nucleotide exchange and hydrolysis, and microtubule-protein interactions. (A) α–and β–tubulin each contain a GTP binding pocket (black) at their N and E-sites (1 and 2, respectively), found within the N-terminal domain of the protein. Nucleotide binding is essential for protein folding, heterodimer stability, and microtubule dynamics. The N-site is formed primarily by α-tubulin residues (1, black) and is stabilized by interactions with some β-tubulin residues (not shown). GTP (1, orange) bound to α–tubulin is non-exchangeable because the N-site is buried at the intra-heterodimer interface. The E-site is formed primarily by residues located near the plus-end of β-tubulin (2, black), and also interacts with some α-tubulin residues located at the inter-heterodimer interface (not shown). GTP bound to β-tubulin is eventually hydrolyzed to GDP (2, orange) once heterodimers have incorporated into microtubules, and the energy released causes microtubule disassembly due to protofilament curling (depicted in figure 3). This force is countered by lateral protofilament interactions and the abundance of GTP-bound β-tubulin heterodimers at the microtubule plus-end. (B) Residues found between the N-terminal and intermediate domains of tubulin (yellow) help regulate the stability of the tubulin heterodimer and structural rearrangements coupled to GTP hydrolysis. (C) Longitudinal interactions are mediated by a series of highly conserved residues found at the interfaces between the inter- and intra-heterodimer (light blue), and facilitate the stability of tubulin heterodimers and the assembly of longitudinal protofilaments (cartoon on left). (D) Lateral protofilament interactions are facilitated by residues that flank the sides and inner surface of heterodimers (purple), and are important for “zipping up” the open sheet of longitudinal protofilaments into a hollow tube (cartoon on left). Lateral protofilament interactions also regulate microtubule dynamics following GTP hydrolysis. (E) MAP and motor protein interactions are mediated by external α–helices and adjacent grooves on the outer surface of the microtubule (green). Cartoon on the left depicts motor protein movement and MAP binding along the surface of a microtubule.

3D tubulin schematics were generated using PyMol (PDB: 1JFF). Cartoons labeled “MT” in panels B–E depict the orientation of heterodimers relative to the assembled microtubule. Transparent tubulin in panels C and D are approximations of longitudinal and lateral interactions, respectively, showing adjacent heterodimer subunits within microtubules.