出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/10/24 17:07:14」(JST)
This article may be too technical for most readers to understand. Please help improve this article to make it understandable to non-experts, without removing the technical details. The talk page may contain suggestions. (April 2015) |
Tubulin | |||||||||
---|---|---|---|---|---|---|---|---|---|
kif1a head-microtubule complex structure in atp-form
|
|||||||||
Identifiers | |||||||||
Symbol | Tubulin | ||||||||
Pfam | PF00091 | ||||||||
Pfam clan | CL0442 | ||||||||
InterPro | IPR003008 | ||||||||
PROSITE | PDOC00201 | ||||||||
SCOP | 1tub | ||||||||
SUPERFAMILY | 1tub | ||||||||
|
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).[1] 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.[2]
Tubulin was long thought to be specific to eukaryotes. Recently, however, the prokaryotic cell division protein FtsZ was shown to be related to tubulin.[3]
The Tubulin/FtsZ family, GTPase domain is an evolutionary conserved protein domain.
This GTPase protein domain is found in all tubulin chains,[4] as well as the bacterial FtsZ family of proteins.[3][5] 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.
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.[6]
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.[7] 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.[8] 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:[citation needed]
All drugs that are known to bind to human tubulin bind to β-tubulin.[9] These include paclitaxel, colchicine, and the vinca alkaloids, each of which have a distinct binding site on β-tubulin.[9]
Class III β-tubulin is a microtubule element expressed exclusively in neurons,[10] and is a popular identifier specific for neurons in nervous tissue. It binds colchicine much more slowly than other isotypes of β-tubulin.[11]
β1-tubulin, sometimes called class VI β-tubulin,[12] is the most divergent at the amino acid sequence level.[13] It is expressed exclusively in megakaryocytes and platelets in humans and appears to play an important role in the formation of platelets.[13]
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.[14]
Human β-tubulins subtypes include:[citation needed]
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:
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:[citation needed]
Zeta-tubulin is present only in kinetoplastid protozoa.[1]
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.
Molecular and cellular biology portal |
|
|
|
|
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
リンク元 | 「駆虫薬」「チューブリン」「チュブリン」 |
拡張検索 | 「alpha-tubulin」「gamma-tubulin」「tubulin modulator」 |
antiplatyhelmintic agents | Antitrematodals (schistosomicides) |
binds tubulin | benzimidazole (Triclabendazole#) |
acetylcholinesterase inhibitor | phosphonic acid (metrifonate) | ||
Other/unknown | quinoline (praziquantel#, oxamniquine#) · phenol (bithionol) · thiazole ([[niridazole]) · arylsulfonate (stibophen) | ||
anticestodals (taeniacides) |
binds tubulin | benzimidazole (albendazole#) | |
Other/unknown | salicylanilide (niclosamide)# · aminoacridine (quinacrine) · butyrophenone (desaspidin) · chlorophenol (dichlorophen) | ||
antinematodal agents (macrofilaricides) |
binds tubulin | benzimidazole (mebendazole#, thiabendazole, albendazole#, fenbendazole, ciclobendazole, flubendazole) | |
chloride channel | macrolide (ivermectin#) | ||
NMDA | tetrahydropyrimidine (pyrantel#, pyrantel pamoate, oxantel) | ||
Other/unknown | piperazine (piperazine · diethylcarbamazine#) · thiazole (levamisole#) · quinolinium (pyrvinium) · benzylammonium (bephenium) · naphthalenesulfonate (suramin#) · tribendimidine |
.