The Fibrous Proteins

Drawing representing the antiparallel-chain pleated-sheet structure. 

Human hair contains about 12 percent of cystine, the double amino acid with two amino-acid groups connected by an S—S bond. For many cystine residues the two ends are in adjacent polypeptide chains, rather than in the same chain. This extensive cross-linking binds the entire hair together, explaining the insolubility of the protein in water, salt solution, and other solvents. If, however, the hair is treated with a reducing agent. 

The hair treated in this way becomes soluble and pliable. It can, for example, be curled, and then set by application of an oxidizing agent. Because of the insolubility of keratin most animals are unable to digest wool. An exception is the clothes moth, which has a high concentration of hydrosulfides in its digestive system. 

After some of the disulfide bonds are broken hair can be stretched to a little over twice its normal length. It then gives a pleated-sheet x-ray pattern. The structure seems to be that of the parallel-chain pleated sheet (length per residue along the chain axis 325 pm, 2.17 times that for the a-helix), rather than of the antiparallel-chain pleated sheet (length per residue 350 pm, 2.33 times that for the a-helix). 

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Proteins are usually separated into two distinct functional classes passive structural materials, which are built up from long fibers, and active components of cellular machinery in which the protein chains are arranged in small compact domains, as we have discussed in earlier chapters. In spite of their differences in structure and function, both these classes of proteins contain a helices and/or p sheets separated by regions of irregular structure. In most cases the fibrous proteins contain specific repetitive amino acid sequences that are necessary for their specific three-dimensional structure. 

Fig. 3. Structure and sequence of repeats present in the fibrous proteins discussed in this chapter. (A) The adenovirus triple -spiral. A single repeat of one of the chains is shown as a stick model colored by atom, the other two as a secondary structure cartoon in yellow and orange. Amino acids contributing to the hydrophobic core are labeled, as is the glycine in the turn. (B) Triple -spiral sequence repeats. Conserved hydrophobic residues are indicated by a hash sign, the conserved glycine or proline by an asterisk. (C) The T4-hber fold. A single repeat of one of the chains is shown as a stick model colored by atom, the other two as a secondary structure cartoon in yellow and orange. Several of the conserved amino acids are labeled. (D) Repeating sequences present in bacteriophage T4 fiber proteins (Cerritelli et al., 1996). Conserved amino acids are indicated by a small letter conserved hydrophobic residues by a hash sign, and conserved small amino acids by a dot.

The nature of the amino acid residues is of prime importance in the development and maintenance of protein structure. Polypeptide chains composed of simple aliphatic amino acids tend to form helices more readily than do those involving many different amino acids. Sections of a polypeptide chain which are mainly non-polar and hydrophobic tend to be buried in the interior of the molecule away from the interface with water, whereas the polar amino acid residues usually lie on the exterior of a globular protein. The folded polypeptide chain is further stabilized by the presence of disulphide bonds, which are produced by the oxidation of two cysteine residues. Such covalent bonds are extremely important in maintaining protein structure, both internally in the globular proteins and externally in the bonding between adjacent chains in the fibrous proteins. 

The fibrous protein elastin found extensively in connective tissues is unlike collagen in that it occurs in a less well ordered fashion, furthermore, there are quite marked differences seen between the chemical compositions of collagen and elastin. Whereas collagen comprises a very limited number of different amino acids, elastin contains a wider variety, the most abundant being glycine (approximately 30% dry weight), alanine (23%) valine (15%) and proline (12%). 

The pleural tissue is a typical connective tissue that consists mostly of matrix the fibrous proteins (collagen, elastin), and mucopolysaccharides, and a few scattered mesothelial cells, capillaries, venules, and ducts. Anatomists have defined several layers (Fig. 3.4) for each of the pleura. Layers 3 and 5 in Fig. 3.4 contain an abundance of fibrous protein, especially elastin. Both the interstitial (Layer 4) and mesothelial (1 and 2) layers contain capillaries of the vascular system and lymphatic channels. The matrix (ground substance) gives the pleura structural integrity and is responsible for its mechanical properties such as elasticity and distensibility. 

The dermis contains several types of cells, including fibroblasts, fat cells, macrophages, histiocytes, mast cells, and cells associated with the blood vessels and nerves of the skin. The predominant cell is the fibroblast, which is associated with biosynthesis of the fibrous proteins and ground substances such as hyaluronic acid, chondroitin sulfates, and mucopolysaccharides. 

Gelatin is derived from the fibrous protein collagen, which is the principal constituent of animal skin, bone, and connective tissue. Fish skin waste could be used as a potential source to isolate collagen and gelatin. Zhu et al. (2010) evaluated the effect of collagen peptides on markers of metabolic nuclear receptors. 

In addition to the 20 common amino acids, proteins may contain residues created by modification of common residues already incorporated into a polypeptide (Fig. 3-8a). Among these uncommon amino acids are 4-hydroxyproline, a derivative of proline, and 5-hydroxylysine, derived from lysine. The former is found in plant cell wall proteins, and both are found in collagen, a fibrous protein of connective tissues. 6-N-Methyllysine is a constituent of myosin, a contractile protein of muscle. Another important uncommon amino acid is y-carboxyglutamate, found in the bloodclotting protein prothrombin and in certain other proteins that bind Ca2+ as part of their biological function. More complex is desmosine, a derivative of four Lys residues, which is found in the fibrous protein elastin. 

In many cases there are important interactions between protein molecules that may lead to highly organized structures such as the pleated sheet of silk fibroin (Figure 25-13) or the coiling of a helices, as found in a-keratins, the fibrous proteins of hair, horn, and muscles (Figure 25-17). This sort of organization of protein molecules is called quaternary structure and is an important feature of many proteins that associate into dimers, tetramers, and so on. The tetrameric structure of hemoglobin is an important example. 

Fibroin, the fibrous protein found in silk, has a secondary structure called a beta- (/8-) pleated sheet, in which a polypeptide chain doubles back on itself after a hairpin bend. The two sections of the chain on either side of the bend line up in a parallel arrangement held together by hydrogen bonds (Figure 24.8). Although not as common as the a-helix, small pleated-sheet regions are often found in proteins. 

One of the key arguments for neutral site binding is the presence of (3-turns and associated conformations. This puts certain restrains on the structure of the fibrous protein. For elastin, conformations with bound calcium are likely to be inside-out with respect to hydrophobicity. Such structures are acceptable only for molecules functioning in a non-polar environment (cell-membranes) but not for a hydrated elastin fibre. Binding of calcium would stabilize a rigid inside-out conformation437. ... 

In order to bring some order to what is clearly a diverse array of observations, this review has attempted to categorize the repeats. Five such classes have been recognized. Each will be dealt with in turn and appropriate examples presented. No attempt has been made to list the repeats observed in the sequences of all proteins instead, representative examples are presented from the fibrous proteins in particular, and the proteins associated with them, in order to illustrate key features of some of the more interesting structures. First, however, these classes are defined. 

Fibrous proteins represent a substantial subset of the human proteome. They include the filamentous structures found in animal hair that act as a protective and thermoregulatory outer material. They are responsible for specifying much of an animal s skeleton, and connective tissues such as tendon, skin, bone, cornea and cartilage all play an important role in this regard. Fibrous proteins are frequently crucial in locomotion and are epitomised by the muscle proteins myosin and tropomyosin and by elastic structures like titin. Yet again the fibrous proteins include filamentous assemblies, such as actin filaments and microtubules, where these provide supporting structures and tracks for the action of a variety of molecular motors. 

The complete set of three books will provide a compendium of up-to-the-minute information on the entire fibrous protein field. Each Chapter, which is clearly written, fully illustrated and with a comprehensive citation list, is by an acknowledged authority in the field. It is our hope that, together, these books will enable valuable comparisons to be made, they will allow general principles to be elucidated and they will help to take the fibrous protein field forward in good shape into the 21st Century era of post-genomics, molecular medicine and nanoscience. 

This maturation and differentiation process is broadly similar to the process for keratinized epithelium, although obviously cells of keratinized epithelium also show increasing amounts of the fibrous protein, keratin, in the upper layers. 

Proteolytic (protein-cleaving) enzymes also have applications in consumer products. For example, papain (from papaya extract) serves as a meat tenderizer. It cleaves the fibrous proteins, making the meat less tough. 

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