In eukaryotes, there are six members of the tubulin superfamily, although not all are present in all species.[3][4] Both α and β tubulins have a mass of around 50kDa and are thus in a similar range compared toactin (with a mass of ~42 kDa). In contrast, tubulinpolymers (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, severalprokaryotic proteins have been shown to be related to tubulin.[5][6][7][8]
Tubulin is characterized by the evolutionarily conserved Tubulin/FtsZ family,GTPaseprotein domain.
This GTPase protein domain is found in all eukaryotic tubulin chains,[9] as well as thebacterial protein TubZ,[8] thearchaeal protein CetZ,[10] and theFtsZ protein family widespread in bacteria andarchaea.[5][11]
α- and β-tubulin polymerize into dynamic microtubules. Ineukaryotes, microtubules are major components of thecytoskeleton, and function in many processes, including structural support,intracellular transport, andDNA segregation.
Comparison of the architectures of a 5-protofilament bacterial microtubule (left; BtubA in dark blue; BtubB in light-blue) and a 13-protofilament eukaryotic microtubule (right; α-tubulin in white; β-tubulin in black). Seams and start-helices are indicated in green and red, respectively.[13]
Microtubules are assembled fromdimers of α- and β-tubulin. These subunits are slightly acidic, with anisoelectric point between 5.2 and 5.8.[14] Each has amolecular weight of approximately 50 kDa.[15]
To form microtubules, the dimers of α- and β-tubulin bind toGTP and assemble onto the (+) ends of microtubules while in the GTP-bound state.[16] 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 eventuallyhydrolyzes into GDP through inter-dimer contacts along themicrotubule protofilament.[17] 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 thedynamic instability of the microtubule.
Homologs of α- and β-tubulin have been identified in theProsthecobactergenus of bacteria.[6] They are designated BtubA and BtubB to identify them as bacterial tubulins. Both exhibithomology to both α- and β-tubulin.[18] While structurally highly similar to eukaryotic tubulins, they have several unique features, includingchaperone-free folding and weak dimerization.[19]Cryogenic electron microscopy showed that BtubA/B forms microtubulesin vivo, and suggested that these microtubules comprise only five protofilaments, in contrast to eukaryotic microtubules, which usually contain 13.[13] Subsequentin vitro studies have shown that BtubA/B forms four-stranded 'mini-microtubules'.[20]
FtsZ is found in nearly allBacteria andArchaea, where it functions incell 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 ringsin vitro, and forms dynamic filamentsin vivo.
TubZ functions in segregating low copy-numberplasmids during bacterial cell division. The protein forms a structure unusual for a tubulin homolog; two helical filaments wrap around one another.[21] This may reflect an optimal structure for this role since the unrelated plasmid-partitioning proteinParM exhibits a similar structure.[22]
CetZ functions in cell shape changes inpleomorphicHaloarchaea. InHaloferax volcanii, CetZ forms dynamic cytoskeletal structures required for differentiation from a plate-shaped cell form into a rod-shaped form that exhibits swimming motility.[10]
All drugs that are known to bind to human tubulin bind to β-tubulin.[24] These includepaclitaxel,colchicine, and thevinca alkaloids, each of which have a distinct binding site on β-tubulin.[24]
In addition, several anti-worm drugs preferentially target the colchicine site of β-Tubulin in worm rather than in higher eukaryotes. Whilemebendazole still retains some binding affinity to human andDrosophila β-tubulin,[25]albendazole almost exclusively binds to the β-tubulin of worms and other lower eukaryotes.[26][27]
Class III β-tubulin is a microtubule element expressed exclusively inneurons,[28] and is a popular identifier specific for neurons in nervous tissue. It binds colchicine much more slowly than otherisotypes of β-tubulin.[29]
β1-tubulin, sometimes called class VI β-tubulin,[30] is the most divergent at the amino acid sequence level.[31] It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets.[31] When class VI β-tubulin were expressed in mammalian cells, they cause disruption of microtubule network, microtubule fragment formation, and can ultimately cause marginal-band like structures present in megakaryocytes and platelets.[32]
Katanin is a protein complex that severs microtubules at β-tubulin subunits, and is necessary for rapid microtubule transport in neurons and in higher plants.[33]
γ-Tubulin, another member of the tubulin family, is important in thenucleation and polar orientation of microtubules. It is found primarily incentrosomes andspindle 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 asγ-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 adimer 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 bymutation andRNAi studies that have inhibited its correct expression. Besides forming a γ-TuRC to nucleate and organize microtubules, γ-tubulin can polymerize into filaments that assemble into bundles and meshworks.[34]
Delta (δ) and epsilon (ε) tubulin have been found to localize atcentrioles and may play a role in centriole structure and function, though neither is as well-studied as the α- and β- forms.
Zeta-tubulin (IPR004058) 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.[4]
BtubA (Q8GCC5) and BtubB (Q8GCC1) are found in some bacterial species in theVerrucomicrobiota genusProsthecobacter.[6] Their evolutionary relationship to eukaryotic tubulins is unclear, although they may have descended from a eukaryotic lineage bylateral gene transfer.[19][18] Compared to other bacterial homologs, they are much more similar to eukaryotic tubulins. In an assembled structure, BtubB acts like α-tubulin and BtubA acts like β-tubulin.[35]
TubZ (Q8KNP3; pBt156) was identified inBacillus thuringiensis as essential forplasmid maintenance.[8] It binds to a DNA-binding protein called TubR (Q8KNP2; pBt157) to pull the plasmid around.[37]
Phages of the genusPhikzlikevirus, as well as aSerratia phage PCH45, use a shell protein (Q8SDA8) to build anucleus-like structure called the phage nucleus. This structure encloses DNA as well as replication and transcription machinery. It protects phage DNA from host defenses likerestriction enzymes and type ICRISPR-Cas systems. Aspindle-forming tubulin, variously namedPhuZ (B3FK34) andgp187, centers the nucleus in the cell.[38][39]
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 toFtsZ, indicating that OdinTubulin may represent an evolution intermediate between FtsZ and microtubule-forming tubulins.[40]
Nowadays there are many scientific investigations of the acetylation done in some microtubules, specially the one byα-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, speciallyneurological diseases.
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