Intermediate filament

Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate branchiostoma. Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate branchiostoma. Intermediate filaments are composed of a family of related proteins sharing common structural and sequence features. Initially designated 'intermediate' because their average diameter (10 nm) is between those of narrower microfilaments (actin) and wider myosin filaments found in muscle cells, the diameter of intermediate filaments is now commonly compared to actin microfilaments (7 nm) and microtubules (25 nm). Most types of intermediate filaments are cytoplasmic, but one type, Type V is a nuclear lamin. Unlike microtubules, IFs distribution in cells show no good correlation with the distribution of either mitochondria or endoplasmic reticulum. The structure of proteins that form IF was first predicted by computerized analysis of the amino acid sequence of a human epidermal keratin derived from cloned cDNAs. Analysis of a second keratin sequence revealed that the two types of keratins share only about 30% amino acid sequence homology but share similar patterns of secondary structure domains. As suggested by the first model, all IF proteins appear to have a central alpha-helical rod domain that is composed of four alpha-helical segments (named as 1A, 1B, 2A and 2B) separated by three linker regions. The central building block of IFs is a pair of two intertwined proteins that is called a coiled-coil structure. This name reflects the fact that the structure of each protein is helical and the intertwined pair is also a helical structure. Structural analysis of a pair of keratins shows that the two proteins that form the so-called coiled-coil bind by hydrophobic interactions. The charged residues in the central domain do not have a major role in the binding of the pair in the central domain (see Fig. 1 in Hanukoglu and Ezra). Cytoplasmic IF assemble into non-polar unit-length filaments (ULF). Identical ULF associate laterally into staggered, antiparallel, soluble tetramers, which associate head-to-tail into protofilaments that pair up laterally into protofibrils, four of which wind together into an intermediate filament.Part of the assembly process includes a compaction step, in which ULF tighten and assume a smaller diameter. The reasons for this compaction are not well understood, and IF are routinely observed to have diameters ranging between 6 and 12 nm. The N and C-termini of IF proteins are non-alpha-helical regions and show wide variation in their lengths and sequences across IF families. The N-terminal 'head domain' binds DNA. Vimentin heads are able to alter nuclear architecture and chromatin distribution, and the liberation of heads by HIV-1 protease may play an important role in HIV-1 associated cytopathogenesis and carcinogenesis. Phosphorylation of the head region can affect filament stability. The head has been shown to interact with the rod domain of the same protein. C-terminal 'tail domain' shows extreme length variation between different IF proteins.