Myosin actin binding

It seems likely, therefore, that as the bound phosphate molecule is released, the cleft starts to open and the myosin head binds to actin (Figure 14.17d). Release of ADP coincides with a conformational change that fully opens the myosin cleft, causing actin to be tightly bound, and moves the lever arm to the "down" position. Since the myosin head is now strongly bound to actin at one end and covalently linked to the myosin fibril at the other... 

Troponin C Troponin I Troponin T Minor M protein 18 21 31 165 2 M line Ca binding Inhibits actin-myosin interaction Binds to tropomyosin Binds to myosin... 

The cytoskeleton also contains different accessory proteins, which, in accordance with their affinities and functions, are designated as microtubule-associated proteins (MAPs), actin-binding proteins (ABPs), intermediate-filament-associated proteins (IFAPs), and myosin-binding proteins. This chapter is focused on those parts of the cytoskeleton that are composed of microfilaments and microtubules and their associated proteins. The subject of intermediate filaments is dealt with in detail in Volume 2. 

The myosins are a superfamily of proteins that have the ability to convert energy released by ATP is hydrolysis into mechanical work. There are many forms of myosin, all of which have ATPase activity and an actin-binding site that is located... 

The Role of Myosins in Cell Locomotion The Role of Actin-Binding Proteins in Cell Locomotion The Transduction of Extracellular Motility Signals to the Cytoskeleton Lipid Flow and Cell Locomotion The Role of Cell Locomotion in Metastasis Intracellular Motility Microtubule-Based Intracellular Motility... 

Actin is a 42 kDa bent dumbbell-shaped globular monomer which is found in most eukaryotic cells. It is the primary protein of the thin (or actin) filaments. Also, by mass or molarity, actin is the largest constituent of the contractile apparatus, actually reaching millimolar concentrations. Actins from different sources seem to be more similar than myosins from the same sources. Actin binds ATP which is hydrolyzed to ADP, if the monomeric actin polymerizes. The backbone structure of the actin filament is a helix formed by two linear strands of polymerized actins like two strings of actin beads entwined. 

The superstructure of smooth muscle actin filaments is differentiated from those of striated muscle by the absence of the troponins and the lateral organization by association of the filaments with dense bodies instead of with the Z-line. How these differences are encoded is again not at all clear. However, the myofibrillar structure and the alignment of the alternating actin and myosin filaments is apparently due primarily to dense bodies and the actin-actinin macrostructures. As the bent dumbbell shaped actins assemble into filaments they are all oriented in the same direction. The S-1 fragments of myosin will bind to actin filaments in vitro and in... 

Huxley suggested that crossbridges can move out in this way and bind to actin because S-2 of HMM acted as a flexible link between LMM in the thick filament backbone and S-1. This was based on the observation that heavy meromyosin could be digested by chymotrypsin into two further subffagments (Lowey et al., 1966), S-1 and S-2, as described above, and that S-1 contained the ATPase and actin binding sites, whereas S-2 did not moreover, S-2 did not self-aggregate, as did the rod or LMM portion of myosin. 

Although this model is very attractive because of its simplicity, further experiments have shown that there are two problems with it (Eisenberg and Hill, 1985). First, myosin.ATP binds as well to actin as does myosin.ADP.Pj such that there is a rapid equilibrium between actomyosin.ATP and myosin.ATP, and between... 

Figure 49-4. Diagram of a myosin moiecuie showing the two intertwined a-heiices (fibrous portion), the giobuiar region or head (G),the iight chains (L), and the effects of proteoiytic cieavage by trypsin and papain. The giobuiar region (myosin head) contains an actin-binding site and an L chain-binding site and aiso attaches to the remainder of the myosin moiecuie.

Function of calcium Reposition troponin/tropomyosin to uncover myosin binding sites on actin Phosphorylate and activate myosin to bind with actin Phosphorylate and activate myosin to bind with actin... 

Iodoacetyl-LC-biotin has been used to localize the SH thiol of myosin by use of an avidin-biotin complex visualized by electron microscopy (Sutoh et al., 1984) and to determine the spatial relationship between SHj and the actin binding site on the myosin subfragment-1 surface (Yamamoto et al., 1984). 

Yamamoto, K., Sekine, T., and Sutoh, K. (1984) Spatial relationship between SHI and the actin binding site on myosin subfragment-1 surface. FEES Lett. 176, 75-78. 

Figure 4.5. Structure of myosin. Myosin comprises both light and heavy chains. The heavy chains may be cleaved by trypsin to generate light meromyosin (LMM) and heavy mero-myosin (HMM). Papain digestion of HMM yields subfragments SI and S2 each SI fragment contains an ATPase site and an actin-binding site. The light chains modify the activity of the ATPase.

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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