Actin monomer

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.

FIGURE 17.13 The three-dimensional structure of an actin monomer from skeletal muscle. This view shows the two domains (left and right) of actin. 

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... 

Actin thin filaments consist of actin, tropomyosin, and the troponins in a 7 1 1 ratio (Figure 17.15). Each tropomyosin molecule spans seven actin molecules, lying along the thin filament groove, between pairs of actin monomers. 

Proteins that bind to actin monomers and inhibit polymerization are designated as profilins (12—15 kD) (Sun et al., 1995). In addition to functioning as an actin-monomer-sequestering protein, profilin binds at least three other... 

Sun, H-Q., Kwiatkowska, K., Yin, H.L. (1995). Actin monomer binding proteins. Curr. Opin. Cell Biol. 7, 102-110. 

Pj release occurs at a relatively apparent slow rate (kobs = 0.005 s" ), so that the transient intermediate F-ADP-Pj in which P is non-covalently bound, has a life time of 2-3 minutes (Carlier and Pantaloni, 1986 Carlier, 1987). While the y-phosphate cleavage step is irreversible as assessed by 0 exchange studies (Carlier et al., 1987), the release of Pi is reversible. Binding of H2PO4 (Kp 10 M) causes the stabilization of actin filaments and the rate of filament growth varies linearly with the concentration of actin monomer in the presence of Pi (Carlier and Pantaloni, 1988). Therefore, Pi release appears as the elementary step responsible for the destabilization of actin-actin interactions in the filament. 

Figure 4. The Brownian ratchet model of lamellar protrusion (Peskin et al., 1993). According to this hypothesis, the distance between the plasma membrane (PM) and the filament end fluctuates randomly. At a point in time when the PM is most distant from the filament end, a new monomer is able to add on. Consequently, the PM is no longer able to return to its former position since the filament is now longer. The filament cannot be pushed backwards by the returning PM as it is locked into the mass of the cell cortex by actin binding proteins. In this way, the PM is permitted to diffuse only in an outward direction. The maximum force which a single filament can exert (the stalling force) is related to the thermal energy of the actin monomer by kinetic theory according to the following equation ...

Figure 8. (Continued). As described above, the packing of myosin molecules into the thick filament is such that a layer of heads is seen every 14.3 nm, and this reflection is thought to derive from this packing. Off the meridian the 42.9 nm myosin based layer line is shown. This arises from the helical pitch of the thick filament, due to the way in which the myosin molecules pack into the filament. The helical pitch is 42.9 nm. c) Meridional reflections from actin. Actin based layer lines can be seen at 35.5 nm, 5.9 nm and 5.1 nm (1st, 6th, and 7th layer lines)and they all arise from the various helical repeats along the thin filament. Only the 35.5 nm layer line is shown here.The 5.9 nm and 5.1 nm layer lines arise from the monomeric repeat. The 35.5 nm layer line arises from the long pitch helical repeat and is roughly equivalent to seven actin monomers. A meridional spot at 2.8 nm can also be seen, d) The equatorial reflections, 1,0 and 1,1 which arise from the spacings between crystal planes seen in cross section of muscle.

Figure 49-3. Schematic representation of the thin fiiament, showing the spatiai configuration of its three major protein components actin, myosin, and tropomyosin. The upper panei shows individual molecules of G-actin. The middle panel shows actin monomers assembled into F-actin. Individual molecules of tropomyosin (two strands wound around one another) and of troponin (made up of its three subunits) are also shown. The lower panel shows the assembled thin filament, consisting of F-actin, tropomyosin, and the three subunits of troponin (TpC, Tpl, andTpT).

Fragments MFs and nucleates assembly, regulated by Ca2+ Binds actin monomers and regulates MF assembly Binds actin monomers, inhibits MF formation, regulated by selected signal transduction pathways Nucleation of actin MF assembly in cortex and initiation of MF branches... 

Actin filaments are the thinnest of the cytoskeletal filaments, and therefore also called microfilaments. Polymerized actin monomers form long, thin fibers of about 8 nm in diameter. Along with the above-mentioned function of the cytoskeleton, actin interacts with myosin ( thick ) filaments in skeletal muscle fibers to provide the force of muscular contraction. Actin/Myosin interactions also help produce cytoplasmic streaming in most cells. 

Figure 4.1. Actin polymerisation. Actin monomers (G-actin) may reversibly assemble into actin filaments (F-actin). Profilin binds to G actin (to form profilactin) and thus prevents its polymerisation.

Figure 4.2. Control of the assembly of the actin network. The actin network may be regulated by (1) the rate of formation of new nucleation centres (composed of three actin monomers) (2) filament formation from these nucleation centres (3) extension of filaments (4) joining of filaments end to end (5) cross-linking of filaments. All of these steps are reversible.

The initial step in actin polymerisation is the activation of actin monomers by binding to divalent cations, a process that causes a conformational change in the monomer. Such activated actin monomers may then either... 

Figure 4.4. Structure of actin filaments (a) shows the beads on a string appearance of an actin filament. This filament comprises actin monomers, which themselves have a polarity, so that they can only assemble head to tail , as shown in (b) thus, the actin filament is polarised, having a barbed and a pointed end.

Profilin maintains G-actin monomer pool 15 PIP2... 

Contractile proteins which form the myofibrils are of two types myosin ( thick filaments each approximately 12 nm in diameter and 1.5 (im long) and actin ( thin filaments 6nm diameter and 1 (Am in length). These two proteins are found not only in muscle cells but widely throughout tissues being part of the cytoskeleton of all cell types. Filamentous actin (F-actin) is a polymer composed of two entwined chains each composed of globular actin (G-actin) monomers. Skeletal muscle F-actin has associated with it two accessory proteins, tropomyosin and troponin complex which are not found in smooth muscle, and which act to regulate the contraction cycle (Figure 7.1). 

The marine macrolides latrunculin A and the less potent variation latrunculin B (5-25 pg/mL, 60 minutes) bind to actin and disrupt the cytoskeleton at low concentrations (90,91). Their mechanism of action includes binding to and sequestering actin monomers, resulting in filament depolymerization (89). 

Tropomyosin is a long helical molecule (70 kDa) which extends along the long axis of the actin filament (Figure 13.7). Each tropomyosin molecule covers seven actin monomers and plays a central role in the regulation of muscle contraction. 

Figure 13.7 A diagram of the actin helix showing position of the tropomyosin. Both actin chains are flanked by tropomyosin molecules, which are long string-like molecules that span seven actin monomers. The troponin complex is attached to the tropomyosin but is not shown. From this diagram, it should be clear how the tropomyosin molecule can conceal the actin-binding sites for the myosin cross-bridges in the relaxed condition. A small conformational change in tropomyosin exposes the sites for attachment of the cross-bridges.

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