Intermediate filament assembly

Intermediate filaments (IFs) are particularly prominent in the cytoplasm of cells that are subject to mechanical stress. Unlike actin and tubulin, which are globular proteins, the many types of IF protein monomers are all highly elongated fibrous molecules that have an N-terminal head, a central rod domain and a C-terminal tail. Despite substantial progress which has been made over the past few years in the elucidation of the complex expression patterns and clinically relevant phenotypes of IFs, the key question of how these filaments assemble and what the molecular architecture of their distinct assembly intermediates comprises, has still not been answered to the extent that has been achieved for actin filaments or microtubules. Slowly but definitely the basic mechanisms of IF assemblage in vitro are being revealed, however, their structure, assembly and mechanical properties in atomic-level detail remain to be determined. Our proposed model (Fig. 1) compares and combines structural information acquired by different methods to ultimately arrive at a more faithful structural model.

Figure 1: A model of intermediate filament assembly as it proceeds by longitudinal annealing of unit-lenght filaments (top) through their loose ends (middle), followed by compactions of the segmented immature filaments (bottom). The model is overlaid on a transmission electron micrograph of a corresponding assembly mixture of recombinant Xenopus vimentin.

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