F-actin

Schroder R R, Jahn W, Manstein D, Hoimes K C and Spudich J A 1993 Three-dimensionai atomic modei of F-actin decorated with Dictyostelium myosin SI Nature 364 171-4... 

The F-actin helix has 13 molecules of G-actin in six turns of the helix, repeating every 360 A. Oriented gels of actin fibers yield x-ray fiber diffraction patterns to about 6 A resolution. Knowing the atomic structure of G-actin it was possible for the group of Ken Holmes to determine its orientation in the F-actin fiber, and thus arrive at an atomic model of the actin filament that best accounted for the fiber diffraction pattern. 

Figure 14.13 Stmcture of G-actin. Two a/P-domains, (red and green) bind an ATP molecuie between them. Tbis ATP is hydrolyzed when the actin monomer polymerizes to F-actin.

Schroeder, R.R., et. al. Three-dimensional atomic model of F-actin decorated with Dictyostelium myosin SI. Nature 364 171-174, 1993. 

FIGURE 17.14 The helical arrangement of actin monomers in F-actin. The F-actin helix has a pitch of 72 nm and a repeat distance of... 

By binding to F-actin, actin binding proteins (ABPs) stabilize F-actin or regulate its turnover. Known ABPs are proteins such as a-actinin, talin, tensin, filamin, nexilin, fimbrin, and vinculin. 

Cytochalasins B and D are used as tools to study F-actin. Cytochalasins bind to the barbed end of F-actin and block the addition as well as dissociation of G-actin at that end. When applied to cultured cells micromolar concentrations of cytochalasins remove stress fibres and other F-actin structures. 

The interaction with myosin motors enables F-actin to transport molecules as well as to change or maintain the shape of the cell by exerting tension. Thus, myosin-I motors move to the barbed end and can transport cargoes such as vesicles. When immobilized at the cargo site... 

Several agents affect the turnover of F-actin. They are not used therapeutically but serve as experimental tools to study the role of F-actin in cell function. 

The cy tochalasins A, B, C, D, E, and H are found in various species of mould. Mainly cytochalasin B and D are used as experimental tools. Cytochalasin D is 10 times more potent, acting at concentrations between 2 and 35 nM in cell-free systems. Cy tochalasins bind to the barbed end of F-actin and block the addition as well as dissociation of G-actin at that end. At micromolar concentrations, cytochalasin D can bind to G-actin and actin dimers and thus block additional polymerization. When applied to cultured cells, micromolar concentrations of cytochalasins remove stress fibres and other F-actin structures. 

Swinholide A, isolated from the marine sponge Theonella swinhoei, sequesters actin dimers and induces their formation. One molecule of swinholide A binds to one dimer. In addition, swinholide A can sever F-actin by binding to the neighbouring protomers. Increased depolymerization of F-actin has also been reported. 

Several toxins produced by marine sponges cause the destabilization of F-actin. They contain a macrocyclic ring and an aliphatic chain, by which they bind to actin protomers. The toxins that include reidispongiolides,... 

Latrunculins A and B are macrolides from the sponge Latrunculia magnified. Latrunculin A (>50 11M) binds close to the nucleotide binding site of G-actin and blocks the assembly with F-actin without promoting disassembly. 

Phalloidin and phallacidin are cyclic peptides from the mushroom Amanita phalloides that stabilize F-actin. Phalloidin binds to residues 114-118 of an actin protomere and blocks nucleotide exchange without interfering with nucleotide hydrolysis. It enhances the rate of nucleation as well as that of elongation. It slowly penetrates the cell membrane and is used for immunocytochemical localization of F-actin. 

In contrast, jasplakinolide, a cyclodepsipeptide from the marine sponge Jaspis johnstoni, rapidly penetrates the cell membrane. It competes with phalloidin for F-actin binding and has a dissociation constant of approximately 15 nM. It induces actin polymerization and stabilizes pre-existing actin filaments. Dolastatin 11, a depsipeptide from the mollusk Dolabella auricu-laria, induces F-actin polymerization. Its binding site differs from that of phalloidin or jasplakinolide. 

F-actin (also called microfilament or actin filament) is a double-stranded, right-handed helix with 14 actin molecules per strand and turn. F-actin has a diameter of 8 nM and is polarized with a pointed (minus) and a barbed (plus) end. 

Intermediate filaments are present in most animal cells. They are composed of more than 50 proteins which are expressed in a cell-type specific manner. Their diameter is about 10 nm and thus between those of the larger microtubules and the smaller F-actin. They form scaffolds and networks in the cyto- and nucleoplasm. 

Motor proteins move along microtubules or F-actin. The respective motor domains are linked to their cargoes via adaptor proteins. Kinesin motors move only to the plus and dynein motors only to the minus ends of microtubules. Myosin motors move along F-actin. When motors are immobilized at their cargo binding area, they can move microtubules or F-actin, respectively. 

Extrapyramidal Side Effects Extrasynaptic Receptors F-actin... 

The diversity of these subcellular actin structures is remarkable and appears to be determined by the interactions of many actin-binding proteins (ABPs) as well as by changes in the concentrations of intracellular signaling molecules such as Ca and cAMP, by small GTP-binding proteins, and by signals arising from mechanical stress. Approximately 50% of the actin molecules in most animal cells are unpolymerized subunits in the cytosolic pool and exist in a state of dynamic equilibrium with labile F-actin filamentous structures (i.e., new structures are formed while existing structures are renewed) (Hall, 1994). 

Blood platelets are key players in the blood-clotting mechanism. These tiny fragments of cytoplasm are shed into the circulation from the surface of megakaryocytes located in the bone marrow. When the lining of a blood vessel is injured, activated platelets release clotting factors, adhere to each other and to damaged surfaces, and send out numerous filopodia. The shape changes that occur in activated platelets are the result of actin polymerization. Before activation, there are no microfilaments because profilin binds to G-actin and prevents its polymerization. After activation, profilin dissociates from G-actin, and bundles and networks of F-actin filaments rapidly appear within the platelet. 

Probing the Intermediate ADP-P State on F-Actin Using Structural Analogues of P, AIF4 and BeFi, H2O 47... 

Myosin Subftagment-I Interacts With Two G-Actin Molecules Oligomers of G-Actin and S] Are the Second Intennediates in F-Actin-Si Assembly Conclusion... 

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