Intermediate filaments are encoded in the human genome by 70 different genes in at least five subfamilies. The defining feature of IF proteins is the presence of a conserved α-helical rod domain of about 310 residues that has the sequence features of a coiled-coil motif (see Figure 3-9a).

The primary building block of intermediate filaments is a dimer held together through the rod domains, which associate as a coiled coil (Figure 18-48a). These dimers then associate in an offset fashion to make tetramers, in which the two dimers have opposite orientations (Figure 18-48b). Tetramers are assembled end to end and interlocked into long protofilaments. Four protofilaments associate into a protofibril, and four protofibrils associate side to side to generate the 10-nm filament. Thus an intermediate filament has 16 protofilaments in it (Figure 18-48c). Flanking the rod domain of each dimer are nonhelical N- and C-terminal domains of different sizes, characteristic of each IF class (Figure 18-48d). Because the tetramer is symmetric, intermediate filaments have no polarity. This description of the filament is based on its structure rather than its mechanism of assembly: at present it is not yet clear how intermediate filaments are assembled in vivo. Unlike microfilaments and microtubules, there are no known intermediate filament nucleating, sequestering, capping, or filament-severing proteins.