Tubulin in
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
can refer either to the tubulin
protein superfamily
A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...
of
globular protein
In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...
s, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
s, a major component of the
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
.
Microtubules function in many essential cellular processes, including
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
.
Tubulin-binding drugs kill
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
ous cells by inhibiting microtubule dynamics, which are required for
DNA segregation and therefore
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
.
In eukaryotes, there are six members of the tubulin superfamily, although not all are present in all species.
[Turk E, Wills AA, Kwon T, Sedzinski J, Wallingford JB, Stearns ]
"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
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
and are thus in a similar range compared to
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
(with a mass of ~42 kDa). In contrast, tubulin
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
s (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, several
prokaryotic
A prokaryote () is a Unicellular organism, single-celled organism that lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek language, Greek wikt:πρό#Ancient Greek, πρό (, 'before') a ...
proteins have been shown to be related to tubulin.
Characterization
Tubulin is characterized by the evolutionarily conserved Tubulin/FtsZ family,
GTPase
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
.
This GTPase protein domain is found in all eukaryotic tubulin chains,
as well as the
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l protein TubZ,
the
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
l protein CetZ,
and the
FtsZ
FtsZ is a protein encoded by the ''ftsZ'' gene that assembles into a ring at the future site of bacterial cell division (also called the Z ring). FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamen ...
protein family widespread in bacteria and
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
.
Function
Microtubules
![Tubulin Infographic](https://upload.wikimedia.org/wikipedia/commons/9/9d/Tubulin_Infographic.jpg)
α- and β-tubulin polymerize into dynamic microtubules. In
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s, microtubules are one of the major components of the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
, and function in many processes, including structural support,
intracellular transport
Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are dist ...
, and
DNA segregation.
![Comparison of bacterial and eukaryotic microtubules](https://upload.wikimedia.org/wikipedia/commons/f/f1/Comparison_of_bacterial_and_eukaryotic_microtubules.jpg)
Microtubules are assembled from
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
s of α- and β-tubulin. These subunits are slightly acidic, with an
isoelectric point
The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). However, pI is also u ...
between 5.2 and 5.8.
Each has a
molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
of approximately 50 kDa.
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
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
into GDP through inter-dimer contacts along the
microtubule protofilament.
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 Dynamic instability may refer to any of several scientific phenomena:
* Aircraft dynamic modes, including aircraft dynamic instability
*Atmospheric instability, in meteorology
* Dynamic instability of microtubules, in biology
*Firehose instability ...
of the microtubule.
Bacterial microtubules
Homologs of α- and β-tubulin have been identified in the ''
Prosthecobacter
''Prosthecobacter'' is a genus of bacteria from the phylum Verrucomicrobiota with a distinctive characteristic; the presence of tubulin-like genes.
Tubulins, which are components of the microtubule, have never been observed in Gracilicutes bef ...
''
genus
Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...
of bacteria.
They are designated BtubA and BtubB to identify them as bacterial tubulins. Both exhibit
homology
Homology may refer to:
Sciences
Biology
*Homology (biology), any characteristic of biological organisms that is derived from a common ancestor
* Sequence homology, biological homology between DNA, RNA, or protein sequences
*Homologous chrom ...
to both α- and β-tubulin.
While structurally highly similar to eukaryotic tubulins, they have several unique features, including
chaperone-free folding and weak dimerization.
Cryogenic electron microscopy
Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample so ...
showed that BtubA/B forms microtubules ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'', 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'.
DNA segregation
Cell division
Prokaryotic division
FtsZ
FtsZ is a protein encoded by the ''ftsZ'' gene that assembles into a ring at the future site of bacterial cell division (also called the Z ring). FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamen ...
is found in nearly all
Bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and
Archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
, where it functions in
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
, 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
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
'', and forms dynamic filaments ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
''.
TubZ functions in segregating low copy-number
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s during bacterial cell division. The protein forms a structure unusual for a tubulin homolog; two helical filaments wrap around one another. This may reflect an optimal structure for this role since the unrelated plasmid-partitioning protein
ParM Parm or PARM may refer to:
* Parmesan cheese, especially in dishes such as chicken parm
* PARM 1 mine, Panzer-Abwehr Richtmine (German, ''Antitank defense arranging mine'')
* '' Authentic Party of the Mexican Revolution'', Partido Auténtico de l ...
exhibits a similar structure.
Cell shape
CetZ functions in cell shape changes in
pleomorphic Haloarchaea
Haloarchaea (halophilic archaea, halophilic archaebacteria, halobacteria) are a class of the Euryarchaeota, found in water saturated or nearly saturated with salt. Halobacteria are now recognized as archaea rather than bacteria and are one of th ...
. In ''
Haloferax volcanii
''Haloferax volcanii'' is a species of organism in the genus ''Haloferax'' in the Archaea.
Description and significance
Microbiologist Benjamin Elazari Volcani first discovered ''Haloferax volcanii'', a self-named extremophile, in the 1930s. '' ...
'', CetZ forms dynamic cytoskeletal structures required for differentiation from a plate-shaped cell form into a rod-shaped form that exhibits swimming motility.
Types
Eukaryotic
The tubulin superfamily contains six families (alpha-(α), beta-(β), gamma-(γ), delta-(δ), epsilon-(ε), and zeta-(ζ) tubulins).
[NCBI CCD cd2186](_blank)
/ref>
α-Tubulin
Human α-tubulin subtypes include:
* TUBA1A
Tubulin alpha-1A chain is a protein that in humans is encoded by the ''TUBA1A'' gene.
Background
Tubulin alpha-1A chain is an alpha-tubulin that participates in the formation of microtubules - structural proteins that participate in cytoskeletal ...
* TUBA1B
Tubulin alpha-1B chain is a protein that in humans is encoded by the ''TUBA1B'' gene.
Interactions
TUBA1B has been shown to interact with PIK3R1
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the ...
* TUBA1C
Tubulin alpha-1C chain is a protein that in humans is encoded by the ''TUBA1C'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ' ...
* TUBA3C
Tubulin alpha-3C/D chain is a protein that in humans is encoded by the ''TUBA3C'' gene.
Function
Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. T ...
* TUBA3D
* TUBA3E
* TUBA4A
Tubulin alpha-4A chain is a protein that in humans is encoded by the ''TUBA4A'' gene.
Function
Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The ...
* TUBA8
Tubulin alpha-8 chain is a protein that in humans is encoded by the ''TUBA8'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or '' ...
β-Tubulin
All drugs that are known to bind to human tubulin bind to β-tubulin. These include paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
, colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken ...
, and the ''vinca'' alkaloids, each of which have a distinct binding site on β-tubulin.
In addition, several anti-worm drugs preferentially target the colchicine site of β-Tubulin in worm rather than in higher eukaryotes. While mebendazole
Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disease, ...
still retains some binding affinity to human and ''Drosophila'' β-tubulin, albendazole
Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, h ...
almost exclusively binds to the β-tubulin of worms and other lower eukaryotes.
Class III β-tubulin
Class III β-tubulin, otherwise known as βIII-tubulin (β3-tubulin) or β-tubulin III, is a microtubule element of the tubulin family found almost exclusively in neurons, and in testis cells. In humans, it is encoded by the TUBB3 gene.
It is p ...
is a microtubule element expressed exclusively in neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s, 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,[omo sapiens (human)- Gene - NCBI">] 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. 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.
Katanin Katanin is a microtubule-severing AAA protein. It is named after the Japanese sword called a katana. Katanin is a heterodimeric protein first discovered in sea urchins. It contains a 60 kDa ATPase subunit, encoded by ''KATNA1'', which functions ...
is a protein complex that severs microtubules at β-tubulin subunits, and is necessary for rapid microtubule transport in neurons and in higher plants.
Human β-tubulins subtypes include:
* TUBB
Tubulin beta chain is a protein that in humans is encoded by the ''TUBB'' gene.
Interactions
TUBB has been shown to interact with NCOA6 and SYT9.
See also
* Tubulin
Tubulin in molecular biology can refer either to the tubulin protein supe ...
* TUBB1
TUBB1 is a gene that codes for the protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysin ...
* TUBB2A
Tubulin beta-2A chain is a protein that in humans is encoded by the ''TUBB2A'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or '' ...
* TUBB2B
* TUBB2C
Tubulin beta-4B chain formerly known as tubulin beta-2C chain is a protein that in humans is encoded by the ''TUBB4B'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of ...
* TUBB3
* TUBB4
Tubulin beta-4A chain is a protein that in humans is encoded by the ''TUBB4A'' gene. Two tubulin beta-4 chain proteins are encoded in the human genome by the genes TUBB4A (this entry) and TUBB4B. Tubulin is the major constituent of microtubules, ...
* TUBB4Q
* TUBB6
* TUBB8
γ-Tubulin
γ-Tubulin, another member of the tubulin family, is important in the nucleation
In thermodynamics, nucleation is the first step in the formation of either a new thermodynamic phase or structure via self-assembly or self-organization within a substance or mixture. Nucleation is typically defined to be the process that deter ...
and polar orientation of microtubules. It is found primarily in centrosomes
In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progres ...
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
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius 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
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
and RNAi
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...
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.
Human γ-tubulin subtypes include:
* TUBG1
Tubulin, gamma 1 is a protein in humans that is encoded by the TUBG1 gene. This gene encodes a member of the tubulin superfamily. The encoded protein localizes to the centrosome where it binds to microtubules as part of a complex referred to as th ...
* TUBG2
Tubulin gamma-2 chain is a protein that in humans is encoded by the ''TUBG2'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''b ...
Members of the γ-tubulin ring complex:
* TUBGCP2
Gamma-tubulin complex component 2 is a protein that in humans is encoded by the ''TUBGCP2'' gene.
It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome.
See also
*Tubulin
* TUBGCP3
* TUBGCP4
Tubuli ...
* TUBGCP3
Gamma-tubulin complex component 3 is a protein that in humans is encoded by the ''TUBGCP3'' gene. It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome.
See also
*Tubulin
* TUBGCP2
* TUBGCP4
Tubulin, ...
* TUBGCP4
Tubulin, gamma complex associated protein 4 is a protein in humans that is encoded by the TUBGCP4 gene.
It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome.
See also
*Tubulin
Tubulin in molecula ...
* TUBGCP5
Gamma-tubulin complex component 5 is a protein that in humans is encoded by the ''TUBGCP5'' gene.
It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome.
See also
*Tubulin
* TUBGCP2
* TUBGCP3
* TUBGCP4 ...
* TUBGCP6
Gamma-tubulin complex component 6 is a protein that in humans is encoded by the ''TUBGCP6'' gene.
It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome.
See also
* Tubulin
* TUBGCP2
* TUBGCP3
* TUB ...
δ and ε-Tubulin
Delta (δ) and epsilon (ε) tubulin have been found to localize at centriole
In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers (Pinophyta), flowering plants (angiosperms) and most fungi, and a ...
s 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:
* δ-tubulin: TUBD1
Tubulin, delta 1 is a protein in humans that is encoded by the TUBD1 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ...
* ε-tubulin: TUBE1
Tubulin, epsilon 1 is a protein in humans that is encoded by the TUBE1 gene.
This gene encodes a member of the tubulin superfamily. This protein localizes to the centriolar sub-distal appendages that are associated with the older of the two centr ...
ζ-Tubulin
Zeta-tubulin () 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.
Prokaryotic
BtubA/B
BtubA () and BtubB () are found in some bacterial species in the Verrucomicrobiota
Verrucomicrobiota is a phylum of Gram-negative bacteria that contains only a few described species. The species identified have been isolated from fresh water, marine and soil environments and human faeces. A number of as-yet uncultivated species ...
genus ''Prosthecobacter
''Prosthecobacter'' is a genus of bacteria from the phylum Verrucomicrobiota with a distinctive characteristic; the presence of tubulin-like genes.
Tubulins, which are components of the microtubule, have never been observed in Gracilicutes bef ...
''. Their evolutionary relationship to eukaryotic tubulins is unclear, although they may have descended from a eukaryotic lineage by lateral gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring ( reproduction). ...
. 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.
FtsZ
Many bacterial and euryarchaeota
Euryarchaeota (from Ancient Greek ''εὐρύς'' eurús, "broad, wide") is a phylum of archaea. Euryarchaeota are highly diverse and include methanogens, which produce methane and are often found in intestines, halobacteria, which survive extre ...
l cells use FtsZ
FtsZ is a protein encoded by the ''ftsZ'' gene that assembles into a ring at the future site of bacterial cell division (also called the Z ring). FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamen ...
to divide via binary fission
Binary may refer to:
Science and technology Mathematics
* Binary number, a representation of numbers using only two digits (0 and 1)
* Binary function, a function that takes two arguments
* Binary operation, a mathematical operation that t ...
. All chloroplasts
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, ...
and some mitochrondria, both organelles derived from endosymbiosis
An ''endosymbiont'' or ''endobiont'' is any organism that lives within the body or cells of another organism most often, though not always, in a mutualistic relationship.
(The term endosymbiosis is from the Greek: ἔνδον ''endon'' "within" ...
of bacteria, also use FtsZ. It was the first prokaryotic cytoskeletal
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compo ...
protein identified.
TubZ
TubZ (; pBt156) was identified in ''Bacillus thuringiensis
''Bacillus thuringiensis'' (or Bt) is a gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types of moths and butterflie ...
'' as essential for plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
maintenance. It binds to a DNA-binding protein called TubR (; pBt157) to pull the plasmid around.
CetZ
CetZ () is found in the euryarchaeal clades of ''Methanomicrobia
In the taxonomy of microorganisms, the Methanomicrobia are a class of the Euryarchaeota.
Phylogeny
The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Center for Biotechnolo ...
'' and ''Halobacteria
Haloarchaea (halophilic archaea, halophilic archaebacteria, halobacteria) are a class of the Euryarchaeota, found in water saturated or nearly saturated with salt. Halobacteria are now recognized as archaea rather than bacteria and are one of th ...
'', where it functions in cell shape differentiation.
Phage tubulins
Phages of the genus '' Phikzlikevirus'', as well as a ''Serratia
''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Yersiniaceae. According to the List of Prokaryotic names with Standing Nomenclature (LPSN), there are currently 19 species of ''Serratia'' that ar ...
'' phage PCH45, use a shell protein () to build a nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
-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
A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class o ...
and type I CRISPR
CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacte ...
-Cas systems. A spindle
Spindle may refer to:
Textiles and manufacturing
* Spindle (textiles), a straight spike to spin fibers into yarn
* Spindle (tool), a rotating axis of a machine tool
Biology
* Common spindle and other species of shrubs and trees in genus ''Euony ...
-forming tubulin, variously named ''PhuZ'' () and ''gp187'', centers the nucleus in the cell.
Odinarchaeota tubulin
'' 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
FtsZ is a protein encoded by the ''ftsZ'' gene that assembles into a ring at the future site of bacterial cell division (also called the Z ring). FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamen ...
'', indicating that OdinTubulin may represent an evolution intermediate between FtsZ and microtubule-forming tubulins.
Pharmacology
Tubulins are targets for anticancer drugs such as vinblastine
Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...
and vincristine
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...
, and paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
. The anti-worm drugs mebendazole
Mebendazole (MBZ), sold under the brand name Vermox among others, is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm infection, hookworm infections, guinea worm infections, hydatid disease, ...
and albendazole
Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, h ...
as well as the anti-gout
Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...
agent colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken ...
bind to tubulin and inhibit microtubule formation. While the former ultimately lead to cell death in worms, the latter arrests neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
motility and decreases inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
in humans. The anti-fungal drug griseofulvin
Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth.
C ...
targets microtubule formation and has applications in cancer treatment.
Post-translational modifications
When incorporated into microtubules, tubulin accumulates a number of post-translational modifications
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes ...
, many of which are unique to these proteins. These modifications include detyrosination Detyrosination is a form of posttranslational modification that occurs on alpha-tubulin. It consists of the removal of the C-terminal tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids ...
, acetylation
:
In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
, polyglutamylation Polyglutamylation is a form of reversible posttranslational modification of glutamate residues seen for example in alpha and beta tubulins
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or on ...
, polyglycylation Polyglycylation is a form of posttranslational modification of glutamate residues of the carboxyl-terminal region tubulin in certain microtubules (e.g., axonemal) originally discovered in ''Paramecium
''
''Paramecium'' ( , ; also spelled '' ...
, phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
, ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
, sumoylation
In molecular biology, SUMO (Small Ubiquitin-like Modifier) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. This process is called SUMOylation (sometimes w ...
, and palmitoylation
Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typically lipid bilayer, memb ...
. Tubulin is also prone to oxidative modification and aggregation during, for example, acute cellular injury.
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
A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weak ...
.
See also
*Motor protein
Motor proteins are a class of molecular motors that can move along the cytoplasm of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.
Cellular functions ...
*Kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells.
Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzy ...
*Dynein
Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements importa ...
References
External links
*
*
Protocols for tubulin experiments
High-resolution tubulin infographic
{{Authority control
Cytoskeleton proteins