Coiled-coil intermediate filament

Fig. 3 Schematic view of the human vimentin protein and force-strain curves of coiled-coil intermediate filament under tensile loadings, (a) Schematic representation of vimentin structure, (b) Force-strain behaviors of a coiled-coil a-helical structures revealing the loading rate dependency of the molecular-level stiffness under tensile loading. (Reprinted from [66], with kind permission from Springer Science and Business Media), (c) a-p secondary structural transition of coiled-coil a-helix under tensile loading. (Reprinted from [67])...

Ackharow T, Buehler Ml (2007) Superelasticity, energy dissipation and strain harderting of vimentin coiled-coil intermediate filaments atomistic and continuum studies. J Mater Sci 42... 

The leucine zipper DNA-binding proteins, described in Chapter 10, are examples of globular proteins that use coiled coils to form both homo- and heterodimers. A variety of fibrous proteins also have heptad repeats in their sequences and use coiled coils to form oligomers, mainly dimers and trimers. Among these are myosin, fibrinogen, actin cross-linking proteins such as spectrin and dystrophin as well as the intermediate filament proteins keratin, vimentin, desmin, and neurofilament proteins. 

Figure 14.6 A model of intermediate filament construction. The monomer shown in (a) pairs with an identical monomer to form a coiled-coil dimer (b). The dimers then line up to form an antiparallel tetramer (c). Within each tetramer the dimers are staggered with respect to one another, allowing it to associate with another tetramer (d). In the final 10-nm rope-like intermediate filament, tetramers are packed together in a helical array (e).

North, A.C.T., Steinert, RM., Parry, D.A.D. Coiled-coil stutter and link segments in keratin and other intermediate filament molecules a computer modeling study. Proteins 20 174-184, 1994. 

Cytokeratins are members of the intermediate filament class of cytoskeletal proteins. Cytokeratins are a large protein family comprising two subfamilies of polypeptides, i.e. acidic (type I) and basic (type II) ones. Cytokeratin form tetramers, consisting of two type I and two type II polypeptides arranged in pairs of laterally aligned coiled coils. The distribution of the different type I and II cytokeratins in normal epithelia and in carcinomas is differentiation-related and can be used for cell typing and identification. 

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 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). 

A common architecture of intermediate filaments is a staggered head-to-tail and side-by-side association of pairs of the coiled-coil dimers into 2- to 3-nm protofilaments and further association of about eight protofilaments to form the 10-nm intermediate filaments.286 290 296... 

Figure 7-31 A model for the structure of keratin microfibrils of intermediate filaments. (A) A coiled-coil dimer, 45-nm in length. The helical segments of the rod domains are interrupted by three linker regions. The conformations of the head and tail domains are unknown but are thought to be flexible. (B) Probable organization of a protofilament, involving staggered antiparallel rows of dimers. From Jeffrey A. Cohlberg297...

The two-stranded a-helical coiled coil is now recognized as one of natures favorite ways of creating a dimerization motif and has been predicted to occur in a diverse group of over 200 proteins.111 This structure consists of two amphipathic, right-handed a-helices that adopt a left-handed supercoil, analogous to a two-stranded rope where the nonpolar face of each a-helix is continually adjacent to that of the other helix. 2 This structure was first postulated by Crick to explain the X-ray diffraction pattern of a-keratin in the absence of sequence information.Pl The coiled-coil dimerization motif is natures way of creating a rod-like molecule that perhaps plays only a structural role in many fibrous proteins, such as the kmef (keratin, myosin, epidermis, fibrinogen) class 3,4 and the intermediate filament proteins)5 6 ... 

Steinert, P. M., Marekov, L. N., and Parry, D. A. D. (1993c). Diversity of intermediate filament structure Evidence that the alignment of coiled-coil molecules in vimen-tin is different from that in keratin intermediate filaments. J. Biol. Chem. 268, 24916-24925. 

Fig. 1. Schematic diagram of (a) an intermediate filament heterodimer with coiled-coil domains 1A, IB, 2A, and 2B, and noncoiled-coil connecting linkers LI, L12, and L2. A stutter occurs in the heptad substructure at a point close to the center of segment 2B. The N-terminal globular domains (green for Type I and brown for Type II chains) are termed the heads, and the C-terminal domains (red for Type I and orange for Type II chains) are designated the tails. In (b), the heads are shown folded back over the rod domain, where it is believed that this will stabilize segment 1A. In (c), the heads are shown away from the body of the rod domain and in a position where they can interact more easily with other cellular entities. As a consequence, segment 1A may become destabilized and hence unwind to form two separate a-helical strands.

Fig. 4. Schematic diagram of segment IB in intermediate filament chains showing generally conserved features. These include the highly conserved residues L74, L81, and E95 the conserved intra- and interchain ionic interactions represented by solid and dotted lines, respectively the trigger motif (residues 79-91) that acts as a particularly stable region that nucleates coiled-coil formation the site at residue 40 (indicated by an asterisk) of a six heptad insertion in lamin molecules. The entire segment displays a regular disposition of acidic and basic residues, each with a period of about 9.54 residues. These periods are approximately out of phase with one another.

Parry, D. A. D., Steven, A. C., and Steinert, P. M. (1985). The coiled-coil molecules of intermediate filaments consist of two parallel chains in exact axial register. Biochem. Biophys. Res. Commun. 127, 1012-1018. 

Smith, T. A., Strelkov, S. V., Burkhard, P., Aebi, U., and Parry, D. A. D. (2002). Sequence comparisons of intermediate filament chains Evidence of a unique functional/structural role for coiled-coil segment 1A and Linker LI. / Struct. Biol. 137, 128-145. 

Steinert, P. M. (1990). The two-chain coiled-coil molecule of native epidermal keradn intermediate filaments is a Type I-Type II heterodimer. /. Biol. Chem. 265, 8766-8774. 

Figure 2.25. Structure of keratin protofibrils. The diagram illustrates the structure of keratin in intermediate filaments containing a helical sequences. Two coils are wound around each other and then packed into protofilaments. Eight protofilaments are packed into a filament.

Together with actin microfilaments and microtubules, keratin filaments make up the cytoskeleton of vertebrate epithelial cells. Keratins belong to a family of intermediate filament proteins that form a-helical coiled-coil dimers that associate laterally and end to end to form 10 nm diameter filaments. Keratin and actin filaments and microtubules form an integrated cytoskeleton that preserves the shape and structural integrity of the ker-atinocyte as well as serves to transmit mechanical loads. Keratins account for about 30% of the total protein in basal cells. 

Eukaryotes have various DNA molecules, arranged in linear fibers which are repeatedly coiled and folded to produce highly organised chromosomes, and a composite cytoplasm which is divided into distinct compartments and houses a variety of cell organelles (mitochondria, chloroplasts, lysosomes, the endoplasmic reticulum, etc.) the form of the cell is due to an internal cytoskeleton which is made of three different types of filaments (microtubules, microfilaments and intermediate filaments). 

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