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kif1a head-microtubule complex structure in atp-form
Tubulin (tubul- + -in) in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. The tubulin superfamily contains six families of tubulins (alpha-, beta-, gamma-, delta-, epsilon and zeta-tubulins). Tubulin is also used to specifically refer to α-tubulin and β-tubulin, the proteins that make up microtubules in eukaryotic cells. Each has a molecular weight of approximately 50,000 Daltons.
The Tubulin/FtsZ family, GTPase domain is an evolutionary conserved protein domain.
This GTPase protein domain is found in all tubulin chains, as well as the bacterial FtsZ family of proteins. These proteins are involved in polymer formation. Tubulin is the major component of microtubules, while FtsZ is the polymer-forming protein of bacterial cell division that forms part of a ring in the middle of the dividing cell that is required for constriction of the cell membrane and cell envelope to yield two daughter cells. FtsZ can polymerise into tubes, sheets, and rings in vitro, and is ubiquitous in bacteria and archaea.
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. 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.
Human α-tubulin subtypes include:
Class III β-tubulin is a microtubule element expressed exclusively in neurons, and is a popular identifier specific for neurons in nervous tissue. It binds colchicine much more slowly than other isotypes of β-tubulin.
β1-tubulin, sometimes called class VI β-tubulin, is the most divergent at the amino acid sequence level. It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets.
Human β-tubulins subtypes include:
γ-Tubulin, another member of the tubulin family, is important in the nucleation and polar orientation of microtubules. It is found primarily in centrosomes and spindle pole bodies, since these are the areas of most abundant microtubule nucleation. In these organelles, several γ-tubulin and other protein molecules are found in complexes known as γ-tubulin ring complexes (γ-TuRCs), which chemically mimic the (+) end of a microtubule and thus allow microtubules to bind. γ-tubulin also has been isolated as a dimer and as a part of a γ-tubulin small complex (γTuSC), intermediate in size between the dimer and the γTuRC. γ-tubulin is the best understood mechanism of microtubule nucleation, but certain studies have indicated that certain cells may be able to adapt to its absence, as indicated by mutation and RNAi studies that have inhibited its correct expression.
Human γ-tubulin subtypes include:
Members of the γ-tubulin ring complex:
δ and ε-Tubulin
Delta (δ) and epsilon (ε) tubulin have been found to localize at centrioles and may play a role in forming the mitotic spindle during mitosis, though neither is as well-studied as the α- and β- forms.
Human δ- and ε-tubulin subtypes include:
Tubulins are targets for anticancer drugs like Taxol, Tesetaxel and the "Vinca alkaloid" drugs such as vinblastine and vincristine. The anti-gout agent colchicine binds to tubulin and inhibits microtubule formation, arresting neutrophil motility and decreasing inflammation. 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.
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- EC 220.127.116.11
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