Protein Filaments

A number of examples have been studied in recent years, including liquid sulfur [1-3,8] and selenium [4], poly(o -methylstyrene) [5-7], polymer-like micelles [9,11], and protein filaments [12]. Besides their importance for applications, EP pose a number of basic questions concerning phase transformations, conformational and relaxational properties, dynamics, etc. which distinguish them from conventional dead polymers in which the reaction of polymerization has been terminated. EP motivate intensive research activity in this field at present. 

Huxley, H.E. (1963). Electron microscope studies on the structure of natural and synthetic protein filaments from striated muscle. J. Mol. Biol. 7, 281-308. 

Keratins are made of filaments, approximately 10 nm in diameter and hundreds of nanometers in length, via assembly of rod-shaped, coiled-coil proteins. Filament formation is initiated by the creation of a dimer comprising monomeric units 44-54 nm in length. Such dimers may form three types of lateral interactions leading to filament formation from equimolar amounts of acidic and basic dimers. In vitro assembly involves the correct alignment of two, three, or four dimers into a nucleus for further, rapid filament assembly [6]. 

The fifth was a molecular biologist, who smiled sweetly and pointed out that all the others had missed the point. The frog jumps because of the biochemical properties of its muscles. The muscles are largely composed of two interdigitated filamentous proteins, actin and myosin, and they contract because the protein filaments slide past each other. This property of the actin and myosin is dependent on the amino acid composition of the two proteins, and hence on chemical, and thus on physical properties. In the last analysis, the molecular biologist insisted, following James Watson, we are all nothing but subatomic particles. 

A basic structural property of protein filaments is polarity, that is, directionality. Almost all naturally occurring filaments are polar (e.g., F-actin, microtubules, TMV, and so on). The few exceptions are either bipolar, like myosin (Huxley, 1963 Squire, 1981), or nonpolar, like intermediate filaments (Herrmann and Aebi, 2004). One method of determining... 

The cytoskeleton is the collective name for all structural filaments in the cell. The cytoskeletal filaments are involved in establishing cell shape, and providing mechanical strength, locomotion, intracellular transport of organelles and chromosome separation in mitosis and meiosis. The cytoskeleton is made up of three kinds of protein filaments actin filaments (also called microfilaments), intermediate filaments and microtubules. 

The anatomical unit of muscle is an elongated cell called a fibre. Each individual fibre cell consists of myofibrils which are bundles of contractile protein filaments composed of actin and myosin (Figure 7.1). Differences in structure indicate that muscles have evolved to perform particular functions. Although the structure of fibres, myofibrils and filaments of actin and myosin, is similar in all muscle types, their arrangement, action and control allow identification of three tissue types ... 

The main obstacle to percntaneous penetration of water and xenobiotics is the onter-most membrane of the epidermis. This is called the stratum comeum. All entry of substances through the stratum comeum occurs by passive diffusion across several cell layers. The locus of entry varies, depending on the chemical properties of xenobiotics. Polar substances are believed to penetrate cell membranes through the protein filaments nonpolar ones enter through the hpid matrix. Hydration of the stratnm comenm increases its permeability for polar substances. Electrolytes enter mainly in a nonionized form, and thus the pH of the solution applied to the skin affects permeabUity. Many hpophdic substances, such as carbon tetrachloride and organophosphate insecticides, readily penetrate the stratum comeum. Pretreatment of the skin with solvents, snch as dimethyl sulfoxide, methanol, ethanol, hexane, acetone, and, in particular, a mixture of chloroform and methanol, increases permeability of the skin (Loomis, 1978). 

Electron microscopy reveals several types of protein filaments crisscrossing the eukaryotic cell, forming an interlocking three-dimensional meshwork, the cytoskeleton. There are three general types of cytoplasmic filaments— actin filaments, microtubules, and intermediate filaments (Fig. 1-9)—differing in width (from about 6 to 22 nm), composition, and specific function. All types provide structure and organization to the cytoplasm and shape to the cell. Actin filaments and microtubules also help to produce the motion of organelles or of the whole cell. 

Figure 27-24 Structures of RecA protein spiral filaments. (A) RecA protein filament formed on circular duplex DNA in the presence of ATP(Y-S), shadowed with Pt and seen by electron microscopy. (B) Diagram of RecA bound to duplex DNA in the presence of ATP(y-S), as determined by electron microscopy. RecA monomers are shown as spheres, but their exact shape is unknown. (C) Diagram of RecA spiral filament in crystals of RecA protein free of DNA, based on X-ray crystallographic data. Arrows indicated alignment of monomers. From Howard-Flanders, West, and Stasiak.536...

Roberts, T. M., Salmon, E. D., and Stewart, M. (1998). Hydrostatic pressure shows that lamellipodial motility in Ascaris sperm requires membrane-associated major sperm protein filament nucleation and elongation./. Cell Biol. 140, 367-375. 

The transcellular pathway has been discredited as a major pathway, although some polar substances can penetrate the outer surface of the protein filaments of hydrated stratum comeum. The transfollicularpathway is really an invagination of the epidermis into the dermis, and the chemical still has to penetrate the epidermis to be absorbed into the blood stream. This is also a regarded as minor route. Sweat pores are not lined with the stratum comeum layer, but the holes are small, and this route is still considered a minor route for chemical absorption. In general, the epidermal surface is 100 to 1000 times the surface area of skin appendages, and it is likely that only very small and/or polar molecules penetrate the skin via these appendages. 

The wool fiber is composed of protein filaments and consists mainly of keratin with a very complex structure. The amino groups of keratin are of decisive importance for the dyeing process. The amount of basic groups titratable with acid is 850 1 mol per gram of wool fiber. In the acidic and neutral range, carboxyl groups are present largely in the undissociated state. 

In the cytoplasm, and especially subjacent to the plasma membrane, are networks of protein filaments that stabilize the lipid membrane and thus contribute to the maintenance of cell shape. In cells that grow and divide, such as liver cells, the cytoplasm appears to be organized from a region near the nucleus that contains the cell s pair of centrioles (Chap. 5). There are three main types of cytoskeletal filaments (1) microtubules, 25 nm in diameter, composed of organized aggregates of the protein tubulin (Chap. 5) (2) actin filaments, 7 nm in diameter (Chap. 5) and (3) so-called intermediate filaments, 10 nm in diameter (Chap. 5). 

Movement. Muscle contraction is accomplished by the interaction between two types of protein filaments, actin and myosin. Myosin also possesses an enzymatic activity for facilitating the conversion of the chemical energy of ATP into mechanical energy. 

In addition to movement through shunts, polar substances may diffuse through the outer surface of the protein filaments of the hydrated stratum corneum, while nonpolar molecules dissolve in and diffuse through the nonaqueous lipid matrix between the protein filaments. The rate of percutaneous absorption through this intercellular lipid pathway is correlated to the partition coefficient of the penetrant, as presented above in Fick s law. 

Figure 10.4 (A) A schematic of globular actin monomer forming a protein filament, called F-actin. This filament is one of the important components of muscle cells, as well as the cytoskeleton of other cells. (B) Oriented actin filaments inside a fibroblast cell, called stress fibers, seen through a fluorescence microscope. Image obtained from Nguyen et al. [148] and reprinted with permission.

The cellular unit that is active toward the contraction of skeletal muscles, known as the sarcomere, is comprised of alternatively stacked filaments of the proteins actin and myosin. During muscle contraction, the protein filaments slide past each other as a result of a rowing action of the surface myosin heads (Figure 6.69a).[" Hence,... 

Figure 6.69. A biomimetic approach toward skeletal muscle movement. Shown is (a) the stacked protein filaments of the sarcomere and (b) a redox-controlled molecular analogue. Adapted with permission from Liu, Y. Flood, A. H. Bonvallet, P. A. Vignon, S. A. Northrop, B. H. Tseng, H.-R. Jeppesen, J. O. Huang, T. J. Brough, B. Bailer, M. Magonov, S. Solares, S. D. Goddard, W. A. Ho, C.-M. Stoddart, J. F. J. Am. Chem. Soc. 2005, 727, 9745. Copyright 2005 American Chemical Society.

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