Intermediate filaments at a glance.

Eukaryotic cells feature two ubiquitous fibrous cytoskeletal polymers in their cytoplasm: F-actin and microtubules. A third fibrous polymer, intermediate filaments (IFs), appeared more recently in evolution (Fuchs and Cleveland, 1998; Erber et al., 1998). Two common traits define members of the family of IF proteins. First, these proteins exhibit a characteristic tripartite domain organization, a generic version of which is shown in the poster. A centrally located domain of fixed length (either ~310 or ~352 residues) is dominated by α-helical segments featuring long-range heptad repeats of hydrophobic/apolar residues (subdomains 1A, 1B, 2A and 2B). This rod domain features highly conserved signature motifs at its Nand C-terminal extremities (shown as magenta boxes). It is flanked by non-helical head and tail domains, which vary considerably in length and primary structure and contribute significantly to the impressive heterogeneity encountered within this family. Second, IF proteins can selfassemble into cytoskeletal filaments, which usually appear as homogeneous, apolar fibers that have a 10-12 nm diameter upon visualization by negative staining and electron microscopy. Examples of keratin and vimentin filament assemblies reconstituted from purified recombinant proteins are shown in the poster at high and low magnification, respectively. The central rod domain represents a major driving force during the self-assembly of all IF proteins. In addition to contributing to assembly (albeit in an IF-protein-specific fashion), the end domains are important sites of regulation and interaction with other cellular elements. A minimum of 67 functional genes encode IF proteins in the human genome (see accompanying table) (Hesse et al., 2001) and, generally speaking, orthologous genes exhibit highly conserved sequences and regulation in mammals and other higher vertebrates.