Intermediate hair filaments

An individual polypeptide in the a-keratin coiled coil has a relatively simple tertiary structure, dominated by an a-helical secondary structure with its helical axis twisted in a left-handed superhelix. The intertwining of the two a-helical polypeptides is an example of quaternary structure. Coiled coils of this type are common structural elements in filamentous proteins and in the muscle protein myosin (see Fig. 5-29). The quaternary structure of a-keratin can be quite complex. Many coiled coils can be assembled into large supramolecular complexes, such as the arrangement of a-keratin to form the intermediate filament of hair (Fig. 4-1 lb). 

FIGURE 4-11 Structure of hair, (a) Hair a-keratin is an elongated a helix with somewhat thicker elements near the amino and carboxyl termini. Pairs of these helices are interwound in a left-handed sense to form two-chain coiled coils. These then combine in higher-order structures called protofilaments and protofibrils. About four protofibrils—32 strands of a-keratin altogether—combine to form an intermediate filament. The individual two-chain coiled coils in the various substructures also appear to be interwound, but the handedness of the interwinding and other structural details are unknown, (b) A hair is an array of many a-keratin filaments, made up of the substructures shown in (a). 

Norgett, E. E., Hatsell, S. J., Carvajal-Huerta, L., Cabezas, J. C., Common, J., Purkis, P. E., Whittock, N., Leigh, I. M., Stevens, H. P., and Kelsell, D. P. (2000). Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair, and keratoderma. Hum. Mol. Genet. 9, 2761-2766. 

Rothnagel, J. A., and Rogers, G. E. (1986). Trichohyalin, an intermediate filament-associated protein of the hair follicle./. Cell Biol. 102, 1419-1429. 

C -Keratin, which is the primary component of wool and hair, consists of two right-handed o helices intertwined to form a type of left-handed superhelix called an a coiled coil, ot-Keratin is a member of a superfamily of proteins referred to as coiled-coil proteins (Figure 2,43). In these proteins, two or more a helices can entwine to form a verv stable structure, which can have a length of 1000 A (100 nm, or 0.1 jiim) or more. There are approximately 60 members of this family in humans, including intermediate filaments, proteins that contribute to the cell cytoskeleton (internal scaffolding in a cell), and the muscle proteins myosin and tropomyosin (Section 34.2). Members of this family are characterized by a central region of 300 amino acids that contains imperfect repeats ol a sequence of seven amino acids called a heptad repeal. 

Keratins - ot-Keratins are the major proteins of hair and fingernails and a compose a major fraction of animal skin, oi-keratins are classified in the broad group of intermediate filament proteins, which play important structural roles in nuclei, cytoplasm, and cell surfaces. Their secondary structure is composed predominantly of -helices. Figure 6.11 shows the coiled-coil structure of the ot-keratin in hair. The chemical composition of the cysteine residues in ot-keratin affects its macromolecular structure and function. For example, hair has relatively few cysteine cross-links, whereas fingernails have many such cross-links, / -keratins, on the other hand, contain much more pleated sheet secondary strucure than ot-keratins and are found in feathers and scales. 

Keratins, a group of fibrous proteins occurring in wool, hair, hooves, claws, horns and feathers, and also in skin, connective tissues and intermediate filaments. a-Keratins occur in mammals, having around 30 various variants, whereas j3-keratins are found in birds, reptiles, and in the silk of insects and arachnids. a-Keratin forms closely associated pairs of a-helices in which each pair is composed of a type I and a type II keratin chain twisted in parallel into a... 

Figure 1-32. Stereogram of a human hair fiber including intermediate filament-matrix structures.

Electron microscopy takes advantage of the high cystine content of matrix to reveal the fine structure of hair in the following manner. Reduction of the fibers followed by treatment with osmium tetroxide, prior to sectioning, produces a heavily stained matrix revealing the relatively unstained intermediate filaments [94]. 

As indicated above, the macrofibrils in human hair contain subfilamentous structures called intermediate filaments (IF) or microfibrils (microfilaments), arranged in spiral formation in the cortical cells. The radius of each spiral, the macrofibril, is approximately 4,000 angstroms [99], and the width or diameter of an intermediate filament is close to 75 angstroms (see Figure 1-17). 

These dimers aggregate in an antiparallel arrangement to form structural units composed of four protein chains or tetramers [101,102], Seven to ten of these tetramer units are then believed to combine or aggregate into a larger helical structure, forming the intermediate filaments (the microfibril structures) of animal hairs. 

The subunits that constitute the intermediate filaments of hair fibers are polypeptide chains of proteins see Figure 1-33. The coiled sections or the helical domains of these protein chains are approximately 10 angstroms in diameter, including side chains, and are believed to approximate the form of an alpha helix, first proposed by Pauling and Corey [103-105] (see Figures 1-34 and 1-35). 

Other analogous to a twisted rope [112-114], This structure has been routinely referred to as the coiled coil model. The model that is now accepted for animal hairs is the two-strand rope polypeptide described in the section entitled, The Intermediate Filaments in Chapter 2. 

To explain the stretching behavior of hair, many scientists consider hair consisting of only two components, intermediate filaments and matrix ... 

In keratin fibers like human hair and wool fiber, the helical proteins of the intermediate filaments (microfibrils) are oriented parallel to the axis of... 

Recently Swift [120] and others have provided evidence that the nonkeratin portions of hair are also important to fiber swelling. For example. Swift demonstrated by the penetration of fluorescent-labeled proteins in water that a large-order swelling occurs in the nonkeratin regions of hair. The diametral swelling of hair by water from the dry state is about 14 to 16%. On the other hand. X-ray diffraction measurement of inter-intermediate filament separation distances indicates that swelling of only 5.5% occurs... 

The intermediate filament molecules in keratins are composed of two different types of polypeptides designated as Type I (acidic side chains) and Type II (neutral to basic side chains). These chains are coiled about each other forming a two-strand coiled-coil rope thus, each filament requires one acidic polypeptide that coils about a basic polypeptide partner or mate. In human hair, there are at least five of these low-sulfur proteins, two Type... 

The Type I intermediate filament proteins of human hair represent a class of proteins and are about 44 and 46K in molecular weight, whereas the Type... 

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