Actin

Actin (English actin, from Greek ἀκτίς aktis, Ray ') is a structural protein found in all eukaryotic cells. It is a component of the cytoskeleton and one of the five most common proteins in eukaryotes; in muscle, every tenth one actin molecule protein molecule, in other cells, the proportion of 1-5 %. Actin forms strung together as F -actin dynamic actin filaments. These microfilaments serve to stabilize the cell shape, the formation of cell processes, intracellular relocation and directed cellular movements. In multicellular organisms, they become central components for muscle contraction. Changes in the coding for actins genes can lead to muscle and other diseases.

History

Actin was shown for the first time in 1887 by William Dobinson Halliburton experimentally. He studied in analogy to the clotting of blood plasma, the conditions under which proteins in cellular fluids of the muscles change their state form (" coagulate " ), and presented the influence of an extract out, which he described as " myosin - ferment ". Halliburton could not deepen, so that the actual discovery of actin is today attributed Bruno Ferenc Straub, who worked as a research assistant in the laboratory Albert Szent- Gyorgyi at the Institute of Medical Chemistry, University of Szeged in Hungary on proteins in muscle his research.

Straub 1942 developed a new technique for the extraction of muscle proteins, which allowed him to gain significant amounts of relatively pure actin, and which is still used essentially unchanged today. Szent- Gyorgyi was described above, the more viscous form of a slow muscle myosin as the " activated" form and as Straub protein showed the same effect at Myosinlösungen, it was referred to as " actin ". Is called to the mixture and the composition of the two proteins, " actomyosin " then ATP, so its viscosity increases again.

Because of the fighting during the 2nd World War, Szent- Gyorgyi and Straub will not be able to publish their work in Western scientific journals. Not until 1945 that they could publish their theses in the "Acta Scandinavica Physilogica " and the term Actin was so well known in the West. Straub continued his work with actin and reported in 1950 that actin contains bound ATP, which is hydrolyzed during the polymerization of microfilaments to ADP and inorganic phosphate, with the resulting ADP remains bound first. Straub suspected that even the conversion of bound ATP to bound ADP would play a significant role in muscle contraction. In fact, this applies only to smooth muscle, however, as late as 2001 could be detected experimentally.

The sequence of amino acids in the polypeptide chain of actin is fully specified in 1973 by M. Elzinga and employees. The crystal structure of G-actin was shown in 1990 by Kabsch and colleagues. In the same year beating Holmes and colleagues, after they had carried out ( co- ) crystallization experiments with different proteins, a model for F- actin before. The process of co- crystallization has been used repeatedly in the following years, until 2001, the isolated protein was shown crystalline together with ADP. However, there is as yet for the F- actin no X-ray structure analysis at high resolution. Was made ​​possible crystallization of F-actin by using a rhodamine conjugate which prevents polymerization by blocking the amino acid Cys 374. Christine Oriol - Audit succeeded in 1977 to crystallize actin in the absence of actin -binding proteins ( ABP). However, the resulting crystals for the former technique were too small to analyze them further.

Although at the moment is for the actin in filamentous form, the filamentous or F- actin, no high-resolution model before, but could contribute to a more accurate picture of the structure Sawaya and his team in 2008, based on the analysis of different crystals of actin dimers in which two G- actins are connected via different binding sites. The model was refined based thereon by Sawaya and Lorenz on. With methods of cryo-electron and the use of synchrotron radiation was recently a higher resolution can be achieved with the ability to better understand the interactions and conformational changes of G -actin during the transition to F-actin in the formation of actin filaments.

Construction

Actin is encoded by a gene family. Man has six paralogous variants, which differ only in a few amino acids and are expressed in various tissue types; These isoforms are functionally differentiated as alpha-, beta- or gamma- actins.

Actin is a single molecule (monomer) before it is used as a G- actin ( actin globular ) means and has a weight of about 42 kDa ( 375 amino acids). Actin is not more than 15 % difference from algae to humans is one of the most conserved proteins.

Actin filaments

Actin (hereinafter referred to as G- actin monomer ) is polymerized to F- actin, which is the main component of microfilaments. The polymerization process but also the reduction of the filament to G -actin can be very dynamic, depending on the current requirements.

Function

Stability

Actin is a component of the cytoskeleton as a dense, rigid, three-dimensional cortical network beneath the plasma membrane, which is crosslinked by the compound above-mentioned proteins. At certain specific points of the cell, this network tends to occur, for example, in Membranausbuchtungen ( microvilli, pseudopodia, synapses ) and in certain cell contacts ( adherens junctions, tight junctions ) and thus contribute to the shape and stability of cells and tissues.

Anchoring and transport distance

Many transmembrane proteins (channels, pumps, receptors, cell adhesion proteins ) are directly or indirectly " tied up " in this cortical actin network held in place. With related functions proteins are kept in close proximity. ( While the long- distance transport of microtubule motor proteins dynein taken with their and kinesin ) Along the Aktinnetzes also takes the short distance transport of vesicles to the membrane by myosin, a class of motor proteins. The myosins take over part of the pilfered from dynein / kinesin charges.

Cell motility

Many eukaryotic cells have a high degree of mobility, cell motility, or cellular migration referred to in order to make, for example, intruders in the body to harmless can ( immune system cells ), to heal wounds (eg, skin cells) or to move generally cells ( in the development or single-celled organisms such as amoeba ). This movement is based mainly on two processes: the directed actin polymerization in the moving direction (controlled by a number of regulators that respond to signals from the cell periphery ) and the actin -myosin interaction fibrils (stress fibers ), contractile tension cables by the cell and extend brace forming elements to the substrate. In order to "feel " the cell environment and to initiate a new direction of movement, the formation of cell filopodia and lamellipodia evils such as playing a significant role. These are formed and stabilized by actin filaments.

Contractile structures

The apparatus of all types of muscle contraction, so all macroscopic motion of the body and its internal organs (for example, peristalsis ), based on the actin -myosin interaction. Besides, numerous actin filaments, myosin II and other proteins in large numbers are arranged in a highly ordered manner. For details please refer to the articles on muscle tissue.