Array ( [0] => {{short description|Superfamily of proteins that make up microtubules}} [1] => {{Infobox protein family [2] => | Symbol = Tubulin [3] => | Name = Tubulin [4] => | image = PDB 1ia0 EBI.jpg [5] => | width = [6] => | caption = kif1a head-microtubule complex structure in atp-form [7] => | Pfam = PF00091 [8] => | Pfam_clan = CL0442 [9] => | InterPro = IPR003008 [10] => | SMART = [11] => | PROSITE = PDOC00201 [12] => | MEROPS = [13] => | SCOP = 1tub [14] => | TCDB = [15] => | OPM family = [16] => | OPM protein = [17] => | CAZy = [18] => | CDD = [19] => }} [20] => '''Tubulin''' in [[molecular biology]] can refer either to the tubulin [[protein superfamily]] of [[globular protein]]s, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into [[microtubule]]s, a major component of the [[eukaryotic]] [[cytoskeleton]].{{cite journal | vauthors = Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC | title = The evolution of compositionally and functionally distinct actin filaments | journal = Journal of Cell Science | volume = 128 | issue = 11 | pages = 2009–19 | date = June 2015 | pmid = 25788699 | doi = 10.1242/jcs.165563 | doi-access = free }} Microtubules function in many essential cellular processes, including [[mitosis]]. [[Discovery and development of tubulin inhibitors|Tubulin-binding drugs]] kill [[cancer]]ous cells by inhibiting microtubule dynamics, which are required for [[DNA]] segregation and therefore [[cell division]]. [21] => [22] => [[#Eukaryotic|In eukaryotes]], there are six members of the tubulin superfamily, although not all are present in all species.Findeisen P, Mühlhausen S, Dempewolf S, Hertzog J, Zietlow A, Carlomagno T, Kollmar M [https://www.ncbi.nlm.nih.gov/pubmed/25169981 "Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family"] Genome Biol Evol (2014) '''6''':2274-2288.Turk E, Wills AA, Kwon T, Sedzinski J, Wallingford JB, Stearns T [https://www.ncbi.nlm.nih.gov/pubmed/26234217 "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. 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 [[polymer]]s (microtubules) tend to be much bigger than actin filaments due to their cylindrical nature. [23] => [24] => Tubulin was long thought to be specific to eukaryotes. More recently, however, several [[prokaryotic]] proteins have been shown to be related to tubulin.{{cite journal | vauthors = Nogales E, Downing KH, Amos LA, Löwe J | title = Tubulin and FtsZ form a distinct family of GTPases | journal = Nature Structural Biology | volume = 5 | issue = 6 | pages = 451–8 | date = June 1998 | pmid = 9628483 | doi = 10.1038/nsb0698-451 | s2cid = 5945125 }}{{cite journal | vauthors = Jenkins C, Samudrala R, Anderson I, Hedlund BP, Petroni G, Michailova N, Pinel N, Overbeek R, Rosati G, Staley JT | display-authors = 6 | title = Genes for the cytoskeletal protein tubulin in the bacterial genus Prosthecobacter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 17049–54 | date = December 2002 | pmid = 12486237 | pmc = 139267 | doi = 10.1073/pnas.012516899 | bibcode = 2002PNAS...9917049J | doi-access = free }}{{cite journal | vauthors = Yutin N, Koonin EV | title = Archaeal origin of tubulin | journal = Biology Direct | volume = 7 | pages = 10 | date = March 2012 | pmid = 22458654 | pmc = 3349469 | doi = 10.1186/1745-6150-7-10 | doi-access = free }}{{cite journal | vauthors = Larsen RA, Cusumano C, Fujioka A, Lim-Fong G, Patterson P, Pogliano J | title = Treadmilling of a prokaryotic tubulin-like protein, TubZ, required for plasmid stability in Bacillus thuringiensis | journal = Genes & Development | volume = 21 | issue = 11 | pages = 1340–52 | date = June 2007 | pmid = 17510284 | pmc = 1877747 | doi = 10.1101/gad.1546107 }} [25] => [26] => == Characterization == [27] => [28] => Tubulin is characterized by the evolutionarily conserved Tubulin/FtsZ family, [[GTPase]] [[protein domain]]. [29] => [30] => This GTPase protein domain is found in all eukaryotic tubulin chains,{{cite journal | vauthors = Nogales E, Wolf SG, Downing KH | title = Structure of the alpha beta tubulin dimer by electron crystallography | journal = Nature | volume = 391 | issue = 6663 | pages = 199–203 | date = January 1998 | pmid = 9428769 | doi = 10.1038/34465 | bibcode = 1998Natur.391..199N | s2cid = 4412367 }} as well as the [[bacteria]]l protein TubZ, the [[archaea]]l protein CetZ, and the [[FtsZ]] protein family widespread in bacteria and [[archaea]].{{cite journal | vauthors = Löwe J, Amos LA | title = Crystal structure of the bacterial cell-division protein FtsZ | journal = Nature | volume = 391 | issue = 6663 | pages = 203–6 | date = January 1998 | pmid = 9428770 | doi = 10.1038/34472 | bibcode = 1998Natur.391..203L | s2cid = 4330857 }} [31] => [32] => == Function == [33] => ===Microtubules=== [34] => [35] => {{Main|Microtubule}}[[File:Tubulin Infographic.jpg|alt=Tubulin and Microtubule Metrics Infographic|thumb|500x500px|Tubulin and microtubule metrics {{Cite web|url=https://puresoluble.com/digital-downloads/|title=Digital Downloads|website=PurSolutions|language=en-US|access-date=2020-02-19}}]] [36] => [37] => α- and β-tubulin polymerize into dynamic microtubules. In [[eukaryote]]s, microtubules are one of the major components of the [[cytoskeleton]], and function in many processes, including structural support, [[intracellular transport]], and [[DNA]] segregation. [[File:Comparison of bacterial and eukaryotic microtubules.jpg|thumb|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.{{cite journal | vauthors = Pilhofer M, Ladinsky MS, McDowall AW, Petroni G, Jensen GJ | title = Microtubules in bacteria: Ancient tubulins build a five-protofilament homolog of the eukaryotic cytoskeleton | journal = PLOS Biology | volume = 9 | issue = 12 | pages = e1001213 | date = December 2011 | pmid = 22162949 | pmc = 3232192 | doi = 10.1371/journal.pbio.1001213 | doi-access = free }}]] [38] => [39] => Microtubules are assembled from [[protein dimer|dimer]]s of α- and β-tubulin. These subunits are slightly acidic, with an [[isoelectric point]] between 5.2 and 5.8.{{cite journal | vauthors = Williams RC, Shah C, Sackett D | title = Separation of tubulin isoforms by isoelectric focusing in immobilized pH gradient gels | journal = Analytical Biochemistry | volume = 275 | issue = 2 | pages = 265–7 | date = November 1999 | pmid = 10552916 | doi = 10.1006/abio.1999.4326 }} Each has a [[molecular weight]] of approximately 50 kDa.{{cite web | url = http://www.ebi.ac.uk/ebisearch/search.ebi?db=proteinSequences&t=tubulin | title = tubulin in Protein sequences | work = EMBL-EBI }} [40] => [41] => To form microtubules, the dimers of α- and β-tubulin bind to [[Guanosine triphosphate|GTP]] and assemble onto the (+) ends of microtubules while in the GTP-bound state.{{cite journal | vauthors = Heald R, Nogales E | title = Microtubule dynamics | journal = Journal of Cell Science | volume = 115 | issue = Pt 1 | pages = 3–4 | date = January 2002 | doi = 10.1242/jcs.115.1.3 | pmid = 11801717 | doi-access = free }} 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 [[hydrolysis|hydrolyzes]] into GDP through inter-dimer contacts along the [[Microtubule#Structure|microtubule protofilament]].{{cite journal | vauthors = Howard J, Hyman AA | title = Dynamics and mechanics of the microtubule plus end | journal = Nature | volume = 422 | issue = 6933 | pages = 753–8 | date = April 2003 | pmid = 12700769 | doi = 10.1038/nature01600 | bibcode = 2003Natur.422..753H | s2cid = 4427406 }} 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 [[Microtubule#Dynamic instability|dynamic instability]] of the microtubule. [42] => [43] => ==== Bacterial microtubules ==== [44] => Homologs of α- and β-tubulin have been identified in the ''[[Prosthecobacter]]'' [[genus]] of bacteria. They are designated BtubA and BtubB to identify them as bacterial tubulins. Both exhibit [[Homology (biology)|homology]] to both α- and β-tubulin.{{cite journal | vauthors = Martin-Galiano AJ, Oliva MA, Sanz L, Bhattacharyya A, Serna M, Yebenes H, Valpuesta JM, Andreu JM | display-authors = 6 | title = Bacterial tubulin distinct loop sequences and primitive assembly properties support its origin from a eukaryotic tubulin ancestor | journal = The Journal of Biological Chemistry | volume = 286 | issue = 22 | pages = 19789–803 | date = June 2011 | pmid = 21467045 | pmc = 3103357 | doi = 10.1074/jbc.M111.230094 | doi-access = free }} While structurally highly similar to eukaryotic tubulins, they have several unique features, including [[Chaperone (protein)|chaperone]]-free folding and weak dimerization.{{cite journal | vauthors = Schlieper D, Oliva MA, Andreu JM, Löwe J | title = Structure of bacterial tubulin BtubA/B: evidence for horizontal gene transfer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 26 | pages = 9170–5 | date = June 2005 | pmid = 15967998 | pmc = 1166614 | doi = 10.1073/pnas.0502859102 | bibcode = 2005PNAS..102.9170S | doi-access = free }} [[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. Subsequent ''in vitro'' studies have shown that BtubA/B forms four-stranded 'mini-microtubules'.{{cite journal | vauthors = Deng X, Fink G, Bharat TA, He S, Kureisaite-Ciziene D, Löwe J | title = Prosthecobacter BtubAB show dynamic instability | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 29 | pages = E5950–E5958 | date = July 2017 | pmid = 28673988 | pmc = 5530688 | doi = 10.1073/pnas.1705062114 | doi-access = free }} [45] => [46] => === DNA segregation === [47] => === Cell division === [48] => ==== Prokaryotic division ==== [49] => [[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]]''. [50] => [51] => TubZ functions in segregating low copy-number [[plasmid]]s during bacterial cell division. The protein forms a structure unusual for a tubulin homolog; two helical filaments wrap around one another.{{cite journal | vauthors = Aylett CH, Wang Q, Michie KA, Amos LA, Löwe J | title = Filament structure of bacterial tubulin homologue TubZ | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 46 | pages = 19766–71 | date = November 2010 | pmid = 20974911 | pmc = 2993389 | doi = 10.1073/pnas.1010176107 | bibcode = 2010PNAS..10719766A | doi-access = free }} This may reflect an optimal structure for this role since the unrelated plasmid-partitioning protein [[ParM]] exhibits a similar structure.{{cite journal | vauthors = Bharat TA, Murshudov GN, Sachse C, Löwe J | title = Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles | journal = Nature | volume = 523 | issue = 7558 | pages = 106–10 | date = July 2015 | pmid = 25915019 | pmc = 4493928 | doi = 10.1038/nature14356 | bibcode = 2015Natur.523..106B }} [52] => [53] => === Cell shape === [54] => CetZ functions in cell shape changes in [[Pleomorphism (microbiology)|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.{{cite journal | vauthors = Duggin IG, Aylett CH, Walsh JC, Michie KA, Wang Q, Turnbull L, Dawson EM, Harry EJ, Whitchurch CB, Amos LA, Löwe J | display-authors = 6 | title = CetZ tubulin-like proteins control archaeal cell shape | journal = Nature | volume = 519 | issue = 7543 | pages = 362–5 | date = March 2015 | pmid = 25533961 | pmc = 4369195 | doi = 10.1038/nature13983 | bibcode = 2015Natur.519..362D }} [55] => [56] => == Types == [57] => [58] => === Eukaryotic === [59] => The tubulin superfamily contains six families (alpha-(α), beta-(β), gamma-(γ), delta-(δ), epsilon-(ε), and zeta-(ζ) tubulins).[https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=100015 NCBI CCD cd2186] [60] => [61] => ==== α-Tubulin ==== [62] => [63] => Human α-tubulin subtypes include:{{citation needed|date=October 2013}} [64] => {{div col|colwidth=20em}} [65] => * [[TUBA1A]] [66] => * [[TUBA1B]] [67] => * [[TUBA1C]] [68] => * [[TUBA3C]] [69] => * TUBA3D [70] => * TUBA3E [71] => * [[TUBA4A]] [72] => * [[TUBA8]] [73] => {{Div col end}} [74] => [75] => ==== β-Tubulin ==== [76] => [[File:Tetrachimena Beta Tubulin.png|thumb|right|β-tubulin in ''[[Tetrahymena]]'' sp.]] [77] => [78] => All drugs that are known to bind to human tubulin bind to β-tubulin.{{cite journal | vauthors = Zhou J, Giannakakou P | title = Targeting microtubules for cancer chemotherapy | journal = Current Medicinal Chemistry. Anti-Cancer Agents | volume = 5 | issue = 1 | pages = 65–71 | date = January 2005 | pmid = 15720262 | doi = 10.2174/1568011053352569 }} These include [[paclitaxel]], [[colchicine]], and the [[vinca alkaloid|''vinca'' alkaloids]], each of which have a distinct binding site on β-tubulin. [79] => [80] => 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,{{cite web |title=Mebendazole |url=https://www.drugs.com/monograph/mebendazole.html |publisher=The American Society of Health-System Pharmacists |access-date=August 18, 2015 |website=Drugs.com |url-status=live |archive-url=https://web.archive.org/web/20191211160404/https://www.drugs.com/monograph/mebendazole.html |archive-date=December 11, 2019}} [[albendazole]] almost exclusively binds to the β-tubulin of worms and other lower eukaryotes.{{cite web |title=Albendazole |url=https://www.drugs.com/monograph/albendazole.html |publisher=The American Society of Health-System Pharmacists |access-date=August 18, 2015 |website=Drugs.com |url-status=live |archive-url=https://web.archive.org/web/20150923232451/http://www.drugs.com/monograph/albendazole.html |archive-date=September 23, 2015}}{{cite journal | vauthors = Serbus LR, Landmann F, Bray WM, White PM, Ruybal J, Lokey RS, Debec A, Sullivan W | display-authors = 6 | title = A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia | journal = PLOS Pathogens | volume = 8 | issue = 9 | pages = e1002922 | date = September 2012 | pmid = 23028321 | doi = 10.1371/journal.ppat.1002922 | pmc = 3447747 | doi-access = free }} [81] => [82] => [[Class III β-tubulin]] is a microtubule element expressed exclusively in [[neuron]]s,{{cite journal | vauthors = Karki R, Mariani M, Andreoli M, He S, Scambia G, Shahabi S, Ferlini C | title = βIII-Tubulin: biomarker of taxane resistance or drug target? | journal = Expert Opinion on Therapeutic Targets | volume = 17 | issue = 4 | pages = 461–72 | date = April 2013 | pmid = 23379899 | doi = 10.1517/14728222.2013.766170 | s2cid = 26229777 }} and is a popular identifier specific for neurons in nervous tissue. It binds colchicine much more slowly than other [[Isotype (immunology)|isotypes]] of β-tubulin.{{cite journal | vauthors = Ludueña RF | title = Are tubulin isotypes functionally significant | journal = Molecular Biology of the Cell | volume = 4 | issue = 5 | pages = 445–57 | date = May 1993 | pmid = 8334301 | pmc = 300949 | doi = 10.1091/mbc.4.5.445 }} [83] => [84] => [[TUBB1|β1-tubulin]], sometimes called class VI β-tubulin,{{cite web | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=81027 | title = TUBB1 tubulin, beta 1 class VI [Homo sapiens (human)] | work = Gene - NCBI }} is the most divergent at the amino acid sequence level.{{cite journal | vauthors = Lecine P, Italiano JE, Kim SW, Villeval JL, Shivdasani RA | title = Hematopoietic-specific beta 1 tubulin participates in a pathway of platelet biogenesis dependent on the transcription factor NF-E2 | journal = Blood | volume = 96 | issue = 4 | pages = 1366–73 | date = August 2000 | pmid = 10942379 | url = http://bloodjournal.hematologylibrary.org/cgi/pmidlookup?view=long&pmid=10942379 | display-authors = 1 | doi = 10.1182/blood.V96.4.1366 | doi-access = free }} It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets. 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.{{cite journal | vauthors = Yang H, Ganguly A, Yin S, Cabral F | title = Megakaryocyte lineage-specific class VI β-tubulin suppresses microtubule dynamics, fragments microtubules, and blocks cell division | journal = Cytoskeleton | volume = 68 | issue = 3 | pages = 175–87 | date = March 2011 | pmid = 21309084 | pmc = 3082363 | doi = 10.1002/cm.20503 }} [85] => [86] => [[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.{{cite journal | vauthors = McNally FJ, Vale RD | title = Identification of katanin, an ATPase that severs and disassembles stable microtubules | journal = Cell | volume = 75 | issue = 3 | pages = 419–29 | date = November 1993 | pmid = 8221885 | doi = 10.1016/0092-8674(93)90377-3 | s2cid = 10264319 }} [87] => [88] => Human β-tubulins subtypes include:{{citation needed|date=October 2013}} [89] => {{div col|colwidth=20em}} [90] => * [[TUBB]] [91] => * [[TUBB1]] [92] => * [[TUBB2A]] [93] => * TUBB2B [94] => * [[TUBB2C]] [95] => * [[TUBB3]] [96] => * [[TUBB4]] [97] => * TUBB4Q [98] => * TUBB6 [99] => * TUBB8 [100] => {{Div col end}} [101] => [102] => ==== γ-Tubulin ==== [103] => [[File:Gamma-tubulin ring complex.png|thumb|Γ-tubulin ring complex (γ-TuRC)]] [104] => [105] => γ-Tubulin, another member of the tubulin family, is important in the [[Microtubule nucleation|nucleation]] and polar orientation of microtubules. It is found primarily in [[centrosomes]] and [[spindle pole body|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 [[Microtubule nucleation|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 [[protein dimer|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. Besides forming a γ-TuRC to nucleate and organize microtubules, γ-tubulin can polymerize into filaments that assemble into bundles and meshworks.{{cite journal | vauthors = Chumová J, Trögelová L, Kourová H, Volc J, Sulimenko V, Halada P, Kučera O, Benada O, Kuchařová A, Klebanovych A, Dráber P, Daniel G, Binarová P | title = γ-Tubulin has a conserved intrinsic property of self-polymerization into double stranded filaments and fibrillar networks | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1865 | issue = 5 | pages = 734–748 | date = 2018 | pmid = 29499229 | doi = 10.1016/j.bbamcr.2018.02.009 | s2cid = 4053150 | doi-access = free }} [106] => [107] => Human γ-tubulin subtypes include: [108] => * [[TUBG1]] [109] => * [[TUBG2]] [110] => [111] => Members of the γ-tubulin ring complex: [112] => {{div col|colwidth=20em}} [113] => * [[TUBGCP2]] [114] => * [[TUBGCP3]] [115] => * [[TUBGCP4]] [116] => * [[TUBGCP5]] [117] => * [[TUBGCP6]] [118] => {{Div col end}} [119] => [120] => ==== δ and ε-Tubulin==== [121] => [122] => Delta (δ) and epsilon (ε) tubulin have been found to localize at [[centriole]]s and may play a role in centriole structure and function, though neither is as well-studied as the α- and β- forms. [123] => [124] => Human δ- and ε-tubulin genes include:{{citation needed|date=October 2013}} [125] => * δ-tubulin: [[TUBD1]] [126] => * ε-tubulin: [[TUBE1]] [127] => [128] => ====ζ-Tubulin==== [129] => [130] => Zeta-tubulin ({{InterPro|IPR004058|l=n}}) 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. [131] => [132] => === Prokaryotic === [133] => [134] => ==== BtubA/B ==== [135] => BtubA ({{UniProt|Q8GCC5}}) and BtubB ({{UniProt|Q8GCC1}}) are found in some bacterial species in the [[Verrucomicrobiota]] genus ''[[Prosthecobacter]]''. Their evolutionary relationship to eukaryotic tubulins is unclear, although they may have descended from a eukaryotic lineage by [[lateral gene transfer]]. 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.{{cite journal | vauthors = Sontag CA, Sage H, Erickson HP | title = BtubA-BtubB heterodimer is an essential intermediate in protofilament assembly | journal = PLOS ONE | volume = 4 | issue = 9 | pages = e7253 | date = September 2009 | pmid = 19787042 | doi = 10.1371/journal.pone.0007253 | pmc = 2746283 | bibcode = 2009PLoSO...4.7253S | doi-access = free }} [136] => [137] => ==== FtsZ ==== [138] => Many bacterial and [[euryarchaeota]]l cells use [[FtsZ]] to divide via [[binary fission]]. All [[chloroplasts]] and some [[Mitochondrion|mitochondria]], both organelles derived from [[endosymbiosis]] of bacteria, also use FtsZ.{{cite journal | vauthors = Margolin W | title = FtsZ and the division of prokaryotic cells and organelles | journal = Nature Reviews. Molecular Cell Biology | volume = 6 | issue = 11 | pages = 862–71 | date = November 2005 | pmid = 16227976 | pmc = 4757588 | doi = 10.1038/nrm1745 }} It was the first prokaryotic [[Cytoskeleton|cytoskeletal]] protein identified. [139] => [140] => ==== TubZ ==== [141] => TubZ ({{UniProt|Q8KNP3}}; pBt156) was identified in ''[[Bacillus thuringiensis]]'' as essential for [[plasmid]] maintenance. It binds to a DNA-binding protein called TubR ({{UniProt|Q8KNP2}}; pBt157) to pull the plasmid around.{{cite journal | vauthors = Ni L, Xu W, Kumaraswami M, Schumacher MA | title = Plasmid protein TubR uses a distinct mode of HTH-DNA binding and recruits the prokaryotic tubulin homolog TubZ to effect DNA partition | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 26 | pages = 11763–8 | date = June 2010 | pmid = 20534443 | doi = 10.1073/pnas.1003817107 | pmc = 2900659 | doi-access = free }} [142] => [143] => ==== CetZ ==== [144] => CetZ ({{UniProt|D4GVD7}}) is found in the [[Euryarchaeota|euryarchaeal]] clades of ''[[Methanomicrobia]]'' and ''[[Halobacteriales|Halobacteria]]'', where it functions in cell shape differentiation. [145] => [146] => ==== Phage tubulins ==== [147] => Phages of the genus ''[[Phikzlikevirus]]'', as well as a ''[[Serratia]]'' phage PCH45, use a shell protein ({{UniProt|Q8SDA8}}) to build a [[cell nucleus|nucleus]]-like structure called the phage nucleus. This structure encloses DNA as well as replication and transcription machinery. It protects phage DNA from host defenses like [[restriction enzymes]] and type I [[CRISPR]]-Cas systems. A [[Spindle apparatus|spindle]]-forming tubulin, variously named ''PhuZ'' ({{UniProt|B3FK34}}) and ''gp187'', centers the nucleus in the cell.{{cite journal |last1=Chaikeeratisak |first1=V |last2=Nguyen |first2=K |last3=Egan |first3=ME |last4=Erb |first4=ML |last5=Vavilina |first5=A |last6=Pogliano |first6=J |title=The Phage Nucleus and Tubulin Spindle Are Conserved among Large Pseudomonas Phages. |journal=Cell Reports |date=15 August 2017 |volume=20 |issue=7 |pages=1563–1571 |doi=10.1016/j.celrep.2017.07.064 |pmid=28813669 |pmc=6028189}}{{cite journal |last1=Malone |first1=Lucia M. |last2=Warring |first2=Suzanne L. |last3=Jackson |first3=Simon A. |last4=Warnecke |first4=Carolin |last5=Gardner |first5=Paul P. |last6=Gumy |first6=Laura F. |last7=Fineran |first7=Peter C. |title=A jumbo phage that forms a nucleus-like structure evades CRISPR–Cas DNA targeting but is vulnerable to type III RNA-based immunity |journal=Nature Microbiology |date=9 December 2019 |volume=5 |issue=1 |pages=48–55 |doi=10.1038/s41564-019-0612-5 |pmid=31819217 |biorxiv=10.1101/782524|s2cid=209164667 }} [148] => [149] => ==== Odinarchaeota tubulin ==== [150] => ''[[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. {{cite journal |last1=Akıl |first1=Caner |last2=Ali |first2=Samson |last3= Tran |first3=Linh T. |last4=Gaillard |first4=Jeremie |last5=Li |first5=Wenfei |last6=Hayashida |first6=Kenichi |last7=Hirose |first7=Mika |last8=Kato |first8=Takayuki |last9=Oshima |first9=Atsunori |last10= Fujishima |first10=Kosuke |last11=Blanchoin |first11=Laurent |last12=Narita |first12=Akihiro |last13=Robinson |first13=Robert C. |title=Structure and dynamics of Odinarchaeota tubulin and the implications for eukaryotic microtubule evolution |year=2021 |doi=10.1101/2021.10.22.465531 |biorxiv=10.1101/2021.10.22.465531 |s2cid=239831170 }} [151] => [152] => == Pharmacology == [153] => {{Further|Epothilone#Mechanism of action}} [154] => [155] => Tubulins are targets for anticancer drugs{{cite journal | vauthors = van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R | title = The Catharanthus alkaloids: pharmacognosy and biotechnology | journal = Current Medicinal Chemistry | volume = 11 | issue = 5 | pages = 607–28 | date = March 2004 | pmid = 15032608 | doi = 10.2174/0929867043455846 }}{{cite book|last = Raviña|first = Enrique|title = The evolution of drug discovery: From traditional medicines to modern drugs|year = 2011|publisher = [[John Wiley & Sons]]|isbn = 9783527326693|pages = 157–159|chapter = Vinca alkaloids|chapter-url = https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA157}}{{cite book|chapter = Africa's gift to the world|pages = 46–51|chapter-url = https://books.google.com/books?id=aXGmCwAAQBAJ&pg=PA46|title = Botanical Miracles: Chemistry of Plants That Changed the World|first1 = Raymond|last1 = Cooper|first2 = Jeffrey John|last2 = Deakin|publisher = [[CRC Press]]|year = 2016|isbn = 9781498704304}} such as [[vinblastine]] and [[vincristine]],{{cite journal | vauthors = Keglevich P, Hazai L, Kalaus G, Szántay C | title = Modifications on the basic skeletons of vinblastine and vincristine | journal = Molecules | volume = 17 | issue = 5 | pages = 5893–914 | date = May 2012 | pmid = 22609781 | pmc = 6268133 | doi = 10.3390/molecules17055893 | doi-access = free }}{{cite journal | vauthors = Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guénard D, Guéritte F | title = Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 1 | pages = 134–42 | date = January 2009 | pmid = 19072542 | doi = 10.1021/jm801064y }} and [[paclitaxel]].{{cite book|chapter-url = https://books.google.com/books?id=FfCfFgWenSAC&pg=PA158|title = The Epothilones: An Outstanding Family of Anti-Tumor Agents: From Soil to the Clinic|editor-first = Johann H.|editor-last = Mulzer|editor-link = Johann Mulzer|publisher = [[Springer Science & Business Media]]|year = 2009|isbn = 9783211782071|chapter = Preclinical Pharmacology and Structure-Activity Studies of Epothilones|pages = 157–220|last = Altmann|first = Karl-Heinz}} The [[Anthelmintic|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 granulocyte|neutrophil]] motility and decreases [[inflammation]] in humans. The anti-fungal drug [[griseofulvin]] targets microtubule formation and has applications in cancer treatment. [156] => [157] => == Post-translational modifications == [158] => {{Main|Microtubule#Post-translational modifications}} [159] => [160] => 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.{{cite journal | vauthors = Samson AL, Knaupp AS, Sashindranath M, Borg RJ, Au AE, Cops EJ, Saunders HM, Cody SH, McLean CA, Nowell CJ, Hughes VA, Bottomley SP, Medcalf RL | display-authors = 6 | title = Nucleocytoplasmic coagulation: an injury-induced aggregation event that disulfide crosslinks proteins and facilitates their removal by plasmin | journal = Cell Reports | volume = 2 | issue = 4 | pages = 889–901 | date = October 2012 | pmid = 23041318 | doi = 10.1016/j.celrep.2012.08.026 | doi-access = free }} [161] => [162] => Nowadays there are many scientific investigations of the acetylation done in some microtubules, specially the one by [[Alpha-tubulin N-acetyltransferase|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 disorder|neurological diseases]]. [163] => [164] => == See also == [165] => {{Portal|Biology}} [166] => *[[Motor protein]] [167] => *[[Kinesin]] [168] => *[[Dynein]] [169] => [170] => == References == [171] => {{reflist|32em}} [172] => [173] => == External links == [174] => * {{MeshName|Tubulin}} [175] => * {{EC number|3.6.5.6}} [176] => *[https://puresoluble.com/protocols/ Protocols for tubulin experiments] [177] => *[https://puresoluble.com/digital-downloads/ High-resolution tubulin infographic] [178] => [179] => {{Cytoskeletal Proteins}} [180] => {{GTPases}} [181] => {{Nerve tissue protein}} [182] => [183] => {{Authority control}} [184] => [185] => [[Category:Cytoskeleton proteins]] [] => )
good wiki

Tubulin

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.

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