Protein chains in hair and epidermal keratin IF: structural features and spatial arrangements.

Abstract

Over the past decade the progress made in characterising the structural hierarchy of both the hard and the epidermal keratin intermediate filaments has exceeded all expectations. The origin of much of this progress can be traced back to the quantity of amino acid sequence data that became available in the early/mid 1980s, and their interpretation in terms of a heterodimeric molecular structure. Subdomains were subsequently identified in both the rod and terminal domains, and now the roles of most of these have been determined in principle, if not yet fully in detail. TEM and STEM, together with very revealing crosslinking analyses have also allowed details to be determined of the mechanism by which molecules assemble into oligomers and oligomers into IF. It remains for the three-dimensional packing of keratin molecules in the IF to be elucidated, but even here progress is being made. A particularly exciting development over the last two or three years has been the establishment of the link between keratinopathies and single point nucleotide mutations in keratin genes. Furthermore, the clustering of mutation sites in regions involved in a key structural mode of molecular aggregation has provided, for the first time, an understanding of keratin diseases at the molecular level.