G-Actin (PDB code: 1j6z). The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography ADP and the divalent cation are highlighted. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy

F-Actin; surface representation of 13 subunit repeat based on Ken Holmes' actin filament model

Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells (except for nematode sperm) where it may be present at concentrations of over 100 μM. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex The nematodes or roundworms ( Phylum Nematoda from Greek (nema "thread" + -ode "like" are one of the most common It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans. Conservation refers to a high degree of similarity in orthologous DNA sequences protein sequences, or Protein structures amongst various In Biology, a species is one of the basic units of Biological classification and a Taxonomic rank. Algae ( sing. alga are a large and diverse group of simple typically Autotrophic organisms ranging from Unicellular to Multicellular forms Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus It is the monomeric subunit of microfilaments, one of the three major components of the cytoskeleton, and of thin filaments, which are part of the contractile apparatus in muscle cells. A monomer (from Greek mono "one" and meros "part" is a small Molecule that may become chemically bonded to other Microfilaments (or actin filaments) are the thinnest filaments of the Cytoskeleton found in the cytoplasm of all Eukaryotic cells. cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. Thus, actin participates in many important cellular functions, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape. Motility is a biological term which refers to the ability to move spontaneously and actively consuming energy in the process Cytokinesis is the process whereby the Cytoplasm of a single Eukaryotic cell is divided to form two daughter cells Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions A cell junction is a structure within a tissue of a Multicellular Organism.

Formation of thin filament

Formation of thin filament

Genetics

Principal interactions of structural proteins at cadherin-based adherens junction. Cadherins are a class of type-1 Transmembrane proteins They play important roles in Cell adhesion, ensuring that cells within tissues are bound together Actin filaments are linked to α-actinin and to membrane through vinculin. In mammalian cells vinculin is a membrane-cytoskeletal protein in Focal adhesion plaques that is involved in linkage of Integrin adhesion molecules to the The head domain of vinculin associates to E-cadherin via α-, β-, and γ-catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.

The protein actin is one of the most highly conserved throughout evolution because it interacts with a large number of other proteins, with 80. 2% sequence conservation at the gene level between Homo sapiens and Saccharomyces cerevisiae (a species of yeast), and 95% conservation of the primary structure of the protein product. Conservation refers to a high degree of similarity in orthologous DNA sequences protein sequences, or Protein structures amongst various History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus Saccharomyces cerevisiae is a Species of Budding Yeast. It is perhaps the most useful Yeast owing to its use since ancient times In Biochemistry, the primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms (including

Although most yeasts have only a single actin gene, higher eukaryotes, in general, express several isoforms of actin encoded by a family of related genes. Yeasts are a growth form of eukaryotic Microorganisms classified in the kingdom Fungi, with about 1500 Species currently described Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such A protein isoform is a version of a Protein with only small differences to another isoform of the same protein Mammals have at least six actin isoforms coded by separate genes,^[1] which are divided into three classes (alpha, beta and gamma) according to their isoelectric point. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Beta-actin (gene name ACTB is one of six different Actin isoforms which have been identified in humans The isoelectric point (pI is the PH at which a particular Molecule or surface carries no net electrical charge. In general, alpha actins are found in muscle (α-skeletal, α-aortic smooth, α-cardiac, and γ2-enteric smooth), whereas beta and gamma isoforms are prominent in non-muscle cells (β- and γ1-cytoplasmic). Although the amino acid sequences and in vitro properties of the isoforms are highly similar, these isoforms cannot completely substitute for one another in vivo. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism In vivo ( Latin: within the living means that which takes place inside an organism. ^[2]

The typical actin gene has an approximately 100-nucleotide 5' UTR, a 1200-nucleotide translated region, and a 200-nucleotide 3' UTR. The five prime untranslated region ( 5' UTR) also known as the leader sequence, is a particular section of Messenger RNA (mRNA and the DNA that codes for Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) The three prime untranslated region (3' UTR is a particular section of Messenger RNA (mRNA The majority of actin genes are interrupted by introns, with up to 6 introns in any of 19 well-characterised locations. Introns, derived from the term "intragenic regions" and also called intervening sequence (IVS are DNA regions in a Gene that are not translated into The high conservation of the family makes actin the favoured model for studies comparing the introns-early and introns-late models of intron evolution.

All non-spherical prokaryotes appear to possess genes such as MreB, which encode homologues of actin; these genes are required for the cell's shape to be maintained. The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other MreB is a protein found in bacteria that has been identified as a homologue of Actin, as indicated by similarities in Tertiary structure and conservation In Evolutionary biology, homology has come to mean any similarity between characters that is due to their shared ancestry. The plasmid-derived gene ParM encodes an actin-like protein whose polymerised form is dynamically unstable, and appears to partition the plasmid DNA into the daughter cells during cell division by a mechanism analogous to that employed by microtubules in eukaryotic mitosis. A plasmid is an extra-chromosomal DNA molecule separate from the chromosomal DNA which is capable of replicating independently of the chromosomal DNA Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei ^[3] Actin is found in both smooth and rough endoplasmic reticulums.

Functions

Actin has four main functions in cells :

• To form the most dynamic one of the three subclasses of the cytoskeleton, which gives mechanical support to cells, and hardwires the cytoplasm with the surroundings to support signal transduction. cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm.
• To allow cell motility (see Actoclampin molecular motors). Motility is a biological term which refers to the ability to move spontaneously and actively consuming energy in the process Microfilaments (or actin filaments) are the thinnest filaments of the Cytoskeleton found in the cytoplasm of all Eukaryotic cells.
• In muscle cells to be the scaffold on which myosin proteins generate force to support muscle contraction. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Myosins are a large family of Motor proteins found in Eukaryotic tissues.
• In non-muscle cells as a track for cargo transport myosins [non-conventional myosins] such as myosin V and VI. Non-conventional myosins transport cargo, such as vesicles and organelles, in a directed fashion, using ATP hydrolysis, at a rate much faster than diffusion. A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed Myosin V walks towards the barbed end of actin filaments, while myosin VI walks toward the pointed end. Most actin filaments are arranged with the barbed end toward the cellular membrane and the pointed end toward the cellular interior. This arrangement allows myosin V to be an effective motor for export of cargos, and myosin VI to be an effective motor for import.

Microfilaments

Individual subunits of actin are known as globular actin (G-actin). Microfilaments (or actin filaments) are the thinnest filaments of the Cytoskeleton found in the cytoplasm of all Eukaryotic cells. In Structural biology, a protein subunit or subunit protein is a single Protein Molecule that assembles (or " coassembles " Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in G-actin subunits assemble into long filamentous polymers called F-actin. Biopolymers are a class of Polymers produced by living organisms Two parallel F-actin strands twist around each other in a helical formation, giving rise to microfilaments of the cytoskeleton. Microfilaments measure approximately 7 nm in diameter with a loop of the helix repeating every 37 nm. A nanometre ( American spelling: nanometer, symbol nm) ( Greek: νάνος nanos dwarf; μετρώ metrό count) is a Geometry, a diameter of a Circle is any straight Line segment that passes through the center of the circle and whose Endpoints are on the

Polarity

The polarity of an actin filament can be determined by decorating the microfilament with myosin "S1" fragments, creating barbed (+) and pointed (-) ends on the filament. Myosins are a large family of Motor proteins found in Eukaryotic tissues. An S1 fragment is composed of the head and neck domains of myosin II.

Actomyosin filaments

In muscle, actin is the major component of thin filaments, which, together with the motor protein myosin (which forms thick filaments), are arranged into actomyosin myofibrils. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Motor proteins are a class of Molecular motors that are able to move along the surface of a suitable substrate Myosins are a large family of Motor proteins found in Eukaryotic tissues. Myofibrils (obsolete term sarcostyles) are cylindrical Organelles found within Muscle cells They are bundles of actomyosin filaments These fibrils comprise the mechanism of muscle contraction. A muscles contraction (also known as a muscle twitch or simply twitch) occurs when a Muscle fibre generates tension through the action of Actin Using the hydrolysis of ATP for energy, myosin heads undergo a cycle during which they attach to thin filaments, exerting a tension, and then depending on the load, perform a power stroke that causes the thin filaments to slide past, shortening the muscle. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy

In contractile bundles, the actin-bundling protein alpha-actinin separates each thin filament by ~35 nm. Actinin is a Microfilament protein α-Actinin is necessary for the attachment of Actin filaments to the Z-line membrane in muscle cells This increase in distance allows thick filaments to fit in between and interact, enabling deformation or contraction. In deformation, one end of myosin is bound to the plasma membrane while the other end "walks" toward the plus end of the actin filament. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer This pulls the membrane into a different shape relative to the cell cortex. A cell cortex is made of Actin microfilaments It is attached to the inner face of the Plasma membrane in cells where microfilaments form mesh-like structure much For contraction, the myosin molecule is usually bound to two separate filaments and both ends simultaneously "walk" toward their filament's plus end, sliding the actin filaments closer to each other. This results in the shortening, or contraction, of the actin bundle (but not the filament). This mechanism is responsible for muscle contraction and cytokinesis, the division of one cell into two. Cytokinesis is the process whereby the Cytoplasm of a single Eukaryotic cell is divided to form two daughter cells

Actin polymerization and depolymerization is necessary in chemotaxis and cytokinesis. Chemotaxis, a kind of Taxis, is the phenomenon in which bodily cells bacteria, and other single-cell or Multicellular organisms direct their movements Cytokinesis is the process whereby the Cytoplasm of a single Eukaryotic cell is divided to form two daughter cells Nucleating factors are necessary to stimulate actin polymerization. Also, Actin filaments themselves bind ATP, and hydrolysis of this ATP stimulates destabilization of the polymer.

History

Actin was first observed experimentally in 1887 by W. In scientific inquiry an experiment ( Latin: Ex- periri, "to try out" is a method of investigating particular types of research questions or Year 1887 ( MDCCCLXXXVII) was a Common year starting on Saturday (link will display the full calendar of the Gregorian calendar (or a Common D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin, and that he dubbed "myosin-ferment. "^[4] However, Halliburton was unable to further characterise his findings, and the discovery of actin is credited instead to Brúnó F. Straub, a young biochemist working in Albert Szent-Györgyi's laboratory at the Institute of Medical Chemistry at the University of Szeged, Hungary. Albert Szent-Györgyi de Nagyrápolt ( September 16, 1893 &ndash October 22, 1986) was a Hungarian Physiologist who The University of Szeged is one of the most distinguished universities in Hungary and in Central Europe. Hungary (Magyarország 'mɔɟɔrorsaːg) officially in English the Republic of Hungary ( Magyar Köztársaság, literally Magyar (Hungarian Republic

In 1942, Straub developed a novel technique for extracting muscle protein that allowed him to isolate substantial amounts of relatively-pure actin. Year 1942 ( MCMXLII) was a Common year starting on Thursday (the link will display the full 1942 calendar of the Gregorian calendar. Straub's method is essentially the same as that used in laboratories today. Szent-Gyorgyi had previously described the more viscous form of myosin produced by slow muscle extractions as 'activated' myosin, and, since Straub's protein produced the activating effect, it was dubbed actin. The hostilities of World War II meant that Szent-Gyorgyi and Straub were unable to publish the work in Western scientific journals; it became well-known in the West only in 1945, when it was published as a supplement to the Acta Physiologica Scandinavica. World War II, or the Second World War, (often abbreviated WWII) was a global military conflict which involved a majority of the world's nations, including The term Western world, the West or the Occident ( Latin: occidens -sunset -west as distinct from the Orient) can have multiple meanings For a broader class of publications which include scientific journals see Academic journal. Year 1945 ( MCMXLV) was a Common year starting on Monday (link will display the full calendar ^[5]

Straub continued to work on actin and in 1950 reported that actin contains bound ATP ^[6] and that, during polymerisation of the protein into microfilaments, the nucleotide is hydrolysed to ADP and inorganic phosphate (which remain bound in the microfilament). Year 1950 ( MCML) was a Common year starting on Sunday (link will display the full calendar of the Gregorian calendar. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine A phosphate, an Inorganic chemical, is a salt of Phosphoric acid. Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. In fact, this is true only in smooth muscle, and was not supported through experimentation until 2001. Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder Year 2001 ( MMI) was a Common year starting on Monday according to the Gregorian calendar. ^[7]

The crystal structure of G-actin was solved in 1990 by Kabsch and colleagues. X-ray crystallography is a method of determining the arrangement of Atoms within a Crystal, in which a beam of X-rays strikes a crystal and scatters Year 1990 ( MCMXC) was a Common year starting on Monday (link displays the 1990 Gregorian calendar) ^[8] In the same year a model for F-actin was proposed by Holmes and colleagues. ^[9] The model was derived by fitting a helix of G-actin structures according to low-resolution fiber diffraction data from the filament. Several models of the filament have been proposed since. However there is still no high-resolution X-ray structure of F-actin.

The Listeria bacteria use the cellular machinery to move around inside the host cell, by inducing directed polymerisation of actin by the ActA transmembrane protein, thus pushing the bacterial cell around. Listeria is a Bacterial Genus containing six species Named in honour of Joseph Lister, Listeria species are Gram-positive A transmembrane protein is a Protein that spans the entire Biological membrane.

See also

• MreB - an actin homologue in bacteria
• Motor protein
• ACTA1 - alpha actin 1
• ACTB - beta actin
• ACTG1 - gamma actin 1

References