Quarterly Reviews of Biophysics

Review Article

Intermediate filaments: molecular architecture, assembly, dynamics and polymorphism

David A. D. Parry a1 and Peter M. Steinert a2
a1 Institute of Fundamental Sciences, Massey University, Private Bag 11–222, Palmerston North, New Zealand
a2 Laboratory of Skin Biology, NIAMS, National Institutes of Health, Building 6 Room 425, Bethesda, MD 20892–2752, USA


1. Introduction 100

2. Molecular architecture 107

2.1 Primary structure 108

2.1.1 Homologous regions 109

2.1.2 Chain typing 115

2.1.3 Post-translational modifications 117

2.2 Secondary structure 118

2.2.1 Central rod domain 118

2.2.2 Head and tail domains 119

2.3 Tertiary structure 123

2.3.1 Coiled-coil rod domain 123 Specificity through salt bridges 124 Specificity through apolar interactions 127 A consensus trigger sequence for two-stranded coiled-coils 128

2.3.2 Discontinuities in the rod domain 128 Links 129 Stutter 131

2.3.3 Head and tail domains 131

2.4 Electron microscope observations 133

3. Assembly 136

3.1 Role of the coiled-coil rod domain 137

3.2 Role of end domains 141

3.3 Experimentally induced crosslinks and modes of assembly 145

3.4 Naturally occurring crosslinks for tissue coordination 154

3.5 STEM data 154

4. Quaternary structure 160

4.1 Protofilaments and protofibrils 160

4.2 Head and tail domains 163

4.3 Surface lattice structure 164

4.4 Crystal studies on intermediate filament fragments 168

5. Polymorphism 169

5.1 Variations on a theme 170

5.1.1 Axial structure 170

5.1.2 Lateral structure 171

6. Keratin intermediate filament chains in diseases 172

7. Concluding remarks 175

8. Acknowledgments 176

9. References 176

Three 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.