Intermediate Filaments: Structure and Assembly

Proteins of the intermediate filament (IF) supergene family are ubiquitous structural components that comprise, in a cell type -specific manner, the cytoskeleton proper in animal tissues. All IF proteins show a distinctly organized, extended a-helical conformation prone to form two-stranded coiled coils, which are the basic building blocks of these highly flexible, stressresistant cytoskeletal filaments. IF proteins are highly charged, thus representing versatile polyampholytes with multiple functions. Taking vimentin, keratins, and the nuclear lamins as our prime examples, we present an overview of their molecular and structural parameters. These, in turn, document the ability of IF proteins to form distinct, highly diverse supramolecular assemblies and biomaterials found, for example, at the inner nuclear membrane, throughout the cytoplasm, and in highly complex extracellular appendages, such as hair and nails, of vertebrate organisms. Ultimately, our aim is to set the stage for a more rational understanding of the immediate effects that missense mutations in IF genes have on cellular functions and for their far-reaching impact on the development of the numerous IF diseases caused by them. Outline 1 Introduction 2 The domain organization: Tripartite fibrous proteins 3 Intermediate filament sequencehomology classes: Molecules under construction 4 Intermediate filament proteins are self-assembling components 5 The evolution of IF genes accompanies the generation of new cellular functions 6 Coiled-coil structure and tetramer formation 7 Filament assembly: The unit-length filament paradigm 8 Assembly mechanism and kinetics 9 Quantitative description and kinetic modeling of assembly 10 Mechanical properties of intermediate filaments and network behavior 11 Conclusion