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Superfamily of proteins that make up microtubules

Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α and β tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton. Microtubules function in many essential cellular processes, including mitosis. Tubulin binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division. In eukaryotes, there are six members of the tubulin superfamily, although not all are present in all species. Both α and β tubulins have a mass of around 50 kDa and are thus in a similar range compared to actin (with a mass of ~42 kDa). In contrast, tubulin polymers (microtubules) tend to be much bigger than actin filaments due to their cylindrical nature. Tubulin was long thought to be specific to eukaryotes. More recently, however, several prokaryotic proteins have been shown to be related to tubulin.

α and β tubulin polymerize into dynamic microtubules. In eukaryotes, microtubules are one of the major components of the cytoskeleton, and function in many processes, including structural support, intracellular transport, and DNA segregation. Microtubules are assembled from dimers of α and β tubulin. These subunits are slightly acidic, with an isoelectric point between 5.2 and 5.8. Each has a molecular weight of approximately 50 kDa. To form microtubules, the dimers of α and β tubulin bind to GTP and assemble onto the (+) ends of microtubules while in the GTP bound state. The β tubulin subunit is exposed on the plus end of the microtubule, while the α tubulin subunit is exposed on the minus end. After the dimer is incorporated into the microtubule, the molecule of GTP bound to the β tubulin subunit eventually hydrolyzes into GDP through inter dimer contacts along the microtubule protofilament. The GTP molecule bound to the α tubulin subunit is not hydrolyzed during the whole process. Whether the β tubulin member of the tubulin dimer is bound to GTP or GDP influences the stability of the dimer in the microtubule. Dimers bound to GTP tend to assemble into microtubules, while dimers bound to GDP tend to fall apart; thus, this GTP cycle is essential for the dynamic instability of the microtubule.

Homologs of α and β tubulin have been identified in the Prosthecobacter genus of bacteria. While structurally highly similar to eukaryotic tubulins, they have several unique features, including chaperone free folding and weak dimerization. Cryogenic electron microscopy showed that BtubA/B forms microtubules in vivo, and suggested that these microtubules comprise only five protofilaments, in contrast to eukaryotic microtubules, which usually contain 13.

FtsZ is found in nearly all Bacteria and Archaea, where it functions in cell division, localizing to a ring in the middle of the dividing cell and recruiting other components of the divisome, the group of proteins that together constrict the cell envelope to pinch off the cell, yielding two daughter cells. FtsZ can polymerize into tubes, sheets, and rings in vitro, and forms dynamic filaments in vivo. TubZ functions in segregating low copy number plasmids during bacterial cell division. The protein forms a structure unusual for a tubulin homolog; two helical filaments wrap around one another. This may reflect an optimal structure for this role since the unrelated plasmid partitioning protein ParM exhibits a similar structure.

CetZ functions in cell shape changes in pleomorphic Haloarchaea. In Haloferax volcanii, CetZ forms dynamic cytoskeletal structures required for differentiation from a plate shaped cell form into a rod shaped form that exhibits swimming motility.

The tubulin superfamily contains six families (alpha (α), beta (β), gamma (γ), delta (δ), epsilon (ε), and zeta (ζ) tubulins).

Zeta tubulin is present in many eukaryotes, but missing from others, including placental mammals. It has been shown to be associated with the basal foot structure of centrioles in multiciliated epithelial cells.

Many bacterial and euryarchaeotal cells use FtsZ to divide via binary fission. All chloroplasts and some mitochondria, both organelles derived from endosymbiosis of bacteria, also use FtsZ. It was the first prokaryotic cytoskeletal protein identified.

TubZ (; pBt156) was identified in Bacillus thuringiensis as essential for plasmid maintenance.

CetZ is found in the euryarchaeal clades of Methanomicrobia and Halobacteria, where it functions in cell shape differentiation.

Asgard archaea tubulin from hydrothermal living Odinarchaeota (OdinTubulin) was identified as a genuine tubulin. OdinTubulin forms protomers and protofilaments most similar to eukaryotic microtubules, yet assembles into ring systems more similar to FtsZ, indicating that OdinTubulin may represent an evolution intermediate between FtsZ and microtubule forming tubulins.

Tubulins are targets for anticancer drugs such as vinblastine and vincristine, and paclitaxel. The anti worm drugs mebendazole and albendazole as well as the anti gout agent colchicine bind to tubulin and inhibit microtubule formation. While the former ultimately lead to cell death in worms, the latter arrests neutrophil motility and decreases inflammation in humans. The anti fungal drug griseofulvin targets microtubule formation and has applications in cancer treatment.

When incorporated into microtubules, tubulin accumulates a number of post translational modifications, many of which are unique to these proteins. These modifications include detyrosination, acetylation, polyglutamylation, polyglycylation, phosphorylation, ubiquitination, sumoylation, and palmitoylation. Tubulin is also prone to oxidative modification and aggregation during, for example, acute cellular injury. Nowadays there are many scientific investigations of the acetylation done in some microtubules, specially the one by α tubulin N acetyltransferase (ATAT1) which is being demonstrated to play an important role in many biological and molecular functions and, therefore, it is also associated with many human diseases, specially neurological diseases.