Coiled coil superhelix

In the keratins, large parts of the peptide chain show right-handed a-helical coiling. Two chains each form a left-handed superhelix, as is also seen in myosin (see p. 65). The superhelical keratin dimers join to form tetramers, and these aggregate further to form protofilaments, with a diameter of 3 nm. Finally, eight protofilaments then form an intermediate filament, with a diameter of 10 nm (see p.204). 

The components of the intermediate filaments belong to five related protein families. They are specific for particular cell types. Typical representatives include the cytokeratins, desmin, vimentin, glial fibrillary acidic protein (GFAP), and neurofilament. These proteins all have a rod-shaped basic structure in the center, which is known as a superhelix ( coiled coil see keratin, p. 70). The dimers are arranged in an antiparallel fashion to form tet-ramers. A staggered head-to-head arrangement produces protofilaments. Eight protofilaments ultimately form an intermediary filament. 

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 24-11 Supercoiling of DNA. When the axis of the DNA double helix is coiled on itself, it forms a new helix (superhelix). The DNA superhelix is usually called a supercoil. 

Coiled coils. In a large family of proteins, two right-handed a helices are coiled around each other in a left-handed superhelix (Fig. 2-21).161-167 This coiled coil structure was first suggested by Francis Crick166... 

The idealized structure of the coiled coil has been parameterized by Crick (Figs. 2a and 3). The distance required for the superhelix to complete a full turn is called the pitch (P), and the angle of a helix relative to the superhelical axis is called the pitch angle (n) [also called... 

Fig. 3. Schematic representation of a tetrameric coiled coil, showing the main parameters. 0n marks the center of one a-helix, An the Ca position of a constituent residue, and Cn the superhelix axis n is the u-helix radius, r0 the superhelix radius, a the pitch angle, Q the pairwise helix-crossing angle, ip the positional orientation angle of a residue or phase of the helix, and to is the phase of the supercoil.

A coiled coil is a protein bundle of 2-5 alpha helices wrapped around each other into a superhelix, also called a supercoil (Lupas, 1996a Mason and Arndt, 2004 Lupas and Gruber, 2005). In the simplest form of coiled coil, helical domains of two proteins wind around one another and bind via a distinctive knobs-into-holes pattern whereby an amino acid side chain of one helix (knob) inserts into a space surrounded by four side chains of the facing helix (hole) as first suggested by Francis Crick in 1952 (Lupas, 1996a Lupas and Gruber, 2005). 

Figure 3.34. An a -Helical Coiled Coil. The two helices wind around one another to form a superhelix. Such structures are found in many proteins including keratin in hair, quills, claws, and horns.

To account for the second repeat distance of 5.1 A for a-keratin, we must go to what is properly the tertiary structure, Pauling has suggested that each helix can itself be coiled into a superhelix which has one turn for every 35 turns of the alpha helix. Six of these superhelixes are woven about a seventh, straight helix to form a seven-strand cable.)... 

Structure of tropocollagen. (a) The coiling of three left-handed helices of collagen polypeptides. The dotted lines indicate hydrogen bonds, (b) The right-handed triple-stranded superhelix. The curved arrow indicates the covalent linkage between two chains. [Reproduced with permission from I. Geis and R. E. Dickerson.]... 

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. 

Residues a and d are located in the interior of an a-helical coiled coil, near the axis of the superhelix. Hydrophobic interactions between these side chains contribute to the stability of the coiled coil. 

The core histones form a multi-subunit complex, an octamer, containing two of each core histone with their structured domains forming an approximately cylindrical core and the random coil domains in solution. The cylindrical core is composed of a tetramer of H3 and H4 flanked by a dimer of H2A and H2B on each end. Then 146 bp of DNA wraps around the core histone octamer, forming 1.7 turns of a superhelix. This particle is known as... 

One needs to remember a-helical coiled coils, introduced in Chapter 3 of your textbook (p. 56). Examination of Figure 3.34 (p. 58) suggests that near the axis of the superhelix some amino acid residues are located in the interior (hydrophobic) portion of the molecule. Since this is a long molecule made up of repeating units, one would expect to have hydrophobic side chains at regular intervals in the molecule. 

The third level tertiary structure) corresponds to packing the two a-heUces through an extremely effective hydrophobic interaction, the leucine zipper. Two a-heUces form a very stable structure winding up around each other and thus forming a kind of a superhelix, the so-called coiled-coil. due to the hydrophobic leucine zipper. ... 

Fig. 2 Supramolecular natural polymeric hydrogels discussed in this chapter, (a) Chemical structure of the most-repeated sequence in collagen, forming the a-chain that folds in a three-stranded superhelix [135]. These superhelices bundle to fram the collagen fiber, (b) Representative chemical structure of fibroin and the antiparallel p-sheet formation connected by hydrophilic linkers, (c) Chemical structure of alginic acid, cross-linked by calcium ions (highlighted), (d) Left Top view of two a-helixes of keratin forming a coiled coll by hydrophobic interactions. Right Overview of subsequent formation of the fibril. The left part is adapted from [57] with permission of The Royal Society of Chemistry...

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