Intermediate flament proteins are characterized by a highly variable central rod-shaped domain with strictly conserved globular domains at either end (Fig. 2.49). Although the various classes of intermediate filaments differ in the amino acid sequence of the rod-shaped domain and show some variation in molecular weight, they all share a homologous region that is important in filament self-assembly. Intermediate filaments are assembled from a pair of helical monomers that twist around each other to form coiled-coil dimers. Then, two coiled-coil dimers twist around each other in antiparallel fashion (parallel but pointing in opposite directions) to generate a staggered tetramer of two coiled-coil dimers, thus forming the nonpolarized unit of the intermediate filaments (see Fig. 2.49). Each tetramer, acting as an individual unit, is aligned along the axis of the filament. The ends of the tetramers are bound together to form the free ends of the filament. This assembly process provides a stable, staggered, helical array in which filaments are packed together and additionally stabilized by lateral binding interactions between adjacent tetramers.
Intermediate filaments are a heterogeneous group of cytoskeletal elements found in various cell types.
FIGURE 2.48 • Electron micrograph of the apical part of an epithelial cell demonstrating intermediate flaments. This electron micrograph, obtained using the quick-freeze deep-etch technique, shows the terminal web (TW ) of an epithelial cell and underlying intermediate flaments (IF ). The long, straight actin flament cores or rootlets (R) extending from the microvilli are cross-linked by a dense network of actin flaments containing numerous actin-binding proteins. The network of intermediate flaments can be seen beneath the terminal web anchoring the actin flaments of the microvilli. 47,000. (Reprinted with permission from Hirokawa N, Keller TC 3rd, Chasan R, Mooseker MS. Mechanism of brush border contractility studied by the quick-freeze, deep-etch method. J Cell Biol 1983;96:1325–1336.)
Intermediate filaments are organized into six major classes on the basis of gene structure, protein composition, and cellular distribution (Table 2.3).
 Classes 1 and 2. These are the most diverse groups of intermediate filaments and are called keratins (cytokeratins). These classes contain more than 50 different isoforms and account for most of the intermediate filaments (about 54 genes out of the total of 70 human intermediate filament genes are linked to keratin molecules). Keratins only assemble as heteropolymers; an acid cytokeratin (class 1) and a basic cytokeratin (class 2) molecule form a heterodimer. Each keratin pair is characteristic of a particular type of epithelium; however, some epithelial cells may express more than one pair. Keratin filaments are found in different cells of epithelial origin. According to new nomenclature, keratins are divided into three expression groups: keratins of simple epithelia,
FIGURE 2.49 • Polymerization and structure of intermediate flaments. Intermediate flaments are self-assembled from a pair of monomers that twist around each other in parallel fashion to form a stable dimer. Two coiled-coil dimers then twist around each other in antiparallel fashion to generate a staggered tetramer of two coiled-coil dimers. This tetramer forms the nonpolarized unit of the intermediate flaments. Each tetramer, acting as an individual unit, aligns along the axis of the flament and binds to the free end of the elongating structure. This staggered helical array is additionally stabilized by lateral binding interactions between adjacent tetramers.