Intermediate filaments: molecular architecture, assembly, dynamics and polymorphism

Abstract

1. Introduction 1002. Molecular architecture 1072.1 Primary structure 1082.1.1 Homologous regions 1092.1.2 Chain typing 1152.1.3 Post-translational modifications 1172.2 Secondary structure 1182.2.1 Central rod domain 1182.2.2 Head and tail domains 1192.3 Tertiary structure 1232.3.1 Coiled-coil rod domain 1232.3.1.1 Specificity through salt bridges 1242.3.1.2 Specificity through apolar interactions 1272.3.1.3 A consensus trigger sequence for two-stranded coiled-coils 1282.3.2 Discontinuities in the rod domain 1282.3.2.1 Links 1292.3.2.2 Stutter 1312.3.3 Head and tail domains 1312.4 Electron microscope observations 1333. Assembly 1363.1 Role of the coiled-coil rod domain 1373.2 Role of end domains 1413.3 Experimentally induced crosslinks and modes of assembly 1453.4 Naturally occurring crosslinks for tissue coordination 1543.5 STEM data 1544. Quaternary structure 1604.1 Protofilaments and protofibrils 1604.2 Head and tail domains 1634.3 Surface lattice structure 1644.4 Crystal studies on intermediate filament fragments 1685. Polymorphism 1695.1 Variations on a theme 1705.1.1 Axial structure 1705.1.2 Lateral structure 1716. Keratin intermediate filament chains in diseases 1727. Concluding remarks 1758. Acknowledgments 1769. References 176Three types of intracellular filament have been identified in eukaryotic cells, and together they constitute the key elements of the cytoskeleton. They are the microtubules, the actin-containing microfilaments and the intermediate filaments. The uniqueness of the former two types of filament in cells has been well known for a long time but, in contrast, the intermediate filaments have been a relative new-comer to the scene. The microtubules and the microfilaments have always been easy to distinguish from one another on the grounds of their respective sizes (microtubules are about 25 nm in diameter and microfilaments are about 7–10 nm in diameter). Additionally, microtubules were capable of being disaggregated by the action of colchicine, and microfilaments could be disassembled by other drugs or be decorated with heavy meromyosin to generate arrowhead-like structures. Importantly, in both microtubules and microfilaments the constituent protein subunits were arranged to give the filaments a directionality, and the ability of these filaments to function in vivo depended crucially on this feature of their structure. Microtubules, for example, are involved in mitosis, motility and transport within the cell: each of these functions is clearly a ‘directional’ one. With this background the discovery and characterization of the intermediate filaments can begin.