Tubulin
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Tubulin in
Tubulin was long thought to be specific to eukaryotes. More recently, however, several
Characterization
Tubulin is characterized by the evolutionarily conserved Tubulin/FtsZ family, GTPase protein domain.
This GTPase protein domain is found in all eukaryotic tubulin chains,[8] as well as the bacterial protein TubZ,[7] the archaeal protein CetZ,[9] and the FtsZ protein family widespread in bacteria and archaea.[4][10]
Function
Microtubules
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
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.[15] 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.[16] 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.
Bacterial microtubules
Homologs of α- and β-tubulin have been identified in the Prosthecobacter genus of bacteria.[5] They are designated BtubA and BtubB to identify them as bacterial tubulins. Both exhibit homology to both α- and β-tubulin.[17] While structurally highly similar to eukaryotic tubulins, they have several unique features, including chaperone-free folding and weak dimerization.[18] 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.[12] Subsequent in vitro studies have shown that BtubA/B forms four-stranded 'mini-microtubules'.[19]
DNA segregation
Cell division
Prokaryotic division
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.[20] This may reflect an optimal structure for this role since the unrelated plasmid-partitioning protein ParM exhibits a similar structure.[21]
Cell shape
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.[9]
Types
Eukaryotic
The tubulin superfamily contains six families (alpha-(α), beta-(β), gamma-(γ), delta-(δ), epsilon-(ε), and zeta-(ζ) tubulins).[22]
α-Tubulin
Human α-tubulin subtypes include:[citation needed]
β-Tubulin
All drugs that are known to bind to human tubulin bind to β-tubulin.[23] These include paclitaxel, colchicine, and the vinca alkaloids, each of which have a distinct binding site on β-tubulin.[23]
In addition, several anti-worm drugs preferentially target the colchicine site of β-Tubulin in worm rather than in higher eukaryotes. While mebendazole still retains some binding affinity to human and Drosophila β-tubulin,[24] albendazole almost exclusively binds to the β-tubulin of worms and other lower eukaryotes.[25][26]
Class III β-tubulin is a microtubule element expressed exclusively in neurons,[27] and is a popular identifier specific for neurons in nervous tissue. It binds colchicine much more slowly than other isotypes of β-tubulin.[28]
β1-tubulin, sometimes called class VI β-tubulin,[29] is the most divergent at the amino acid sequence level.[30] It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets.[30] 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.[31]
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.[32]
Human β-tubulins subtypes include:[citation needed]
γ-Tubulin
γ-Tubulin, another member of the tubulin family, is important in the
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 centriole structure and function, though neither is as well-studied as the α- and β- forms.
Human δ- and ε-tubulin genes include:[citation needed]
ζ-Tubulin
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.[3]
Prokaryotic
BtubA/B
BtubA (Q8GCC5) and BtubB (Q8GCC1) are found in some bacterial species in the
FtsZ
Many bacterial and
TubZ
TubZ (Q8KNP3; pBt156) was identified in Bacillus thuringiensis as essential for plasmid maintenance.[7] It binds to a DNA-binding protein called TubR (Q8KNP2; pBt157) to pull the plasmid around.[36]
CetZ
CetZ (D4GVD7) is found in the euryarchaeal clades of Methanomicrobia and Halobacteria, where it functions in cell shape differentiation.[9]
Phage tubulins
Phages of the genus
Odinarchaeota tubulin
Pharmacology
Tubulins are targets for anticancer drugs
Post-translational modifications
When incorporated into microtubules, tubulin accumulates a number of
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.
See also
References
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- ^ Findeisen P, Mühlhausen S, Dempewolf S, Hertzog J, Zietlow A, Carlomagno T, Kollmar M "Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family" Genome Biol Evol (2014) 6:2274-2288.
- ^ a b Turk E, Wills AA, Kwon T, Sedzinski J, Wallingford JB, Stearns T "Zeta-Tubulin Is a Member of a Conserved Tubulin Module and Is a Component of the Centriolar Basal Foot in Multiciliated Cells" Current Biology (2015) 25:2177-2183.
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- ^ "Mebendazole". Drugs.com. The American Society of Health-System Pharmacists. Archived from the original on December 11, 2019. Retrieved August 18, 2015.
- ^ "Albendazole". Drugs.com. The American Society of Health-System Pharmacists. Archived from the original on September 23, 2015. Retrieved August 18, 2015.
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- ^ "TUBB1 tubulin, beta 1 class VI [Homo sapiens (human)]". Gene - NCBI.
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External links
- Tubulin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- EC 3.6.5.6
- Protocols for tubulin experiments
- High-resolution tubulin infographic