| Abstract: | Mammalian epidermal keratin molecules adopt rod-shaped conformations that aggregate to form cytoplasmic intermediate filaments. To investigate these keratin conformations and the basis for their patterns of molecular association, graphical methods were developed to relate known amino acid sequences to probable spacial configurations. The results support the predominantly α-helical conformation of keratin chains, interrupted by short non-α-helical linkages. However, it was found that many of the linkages have amino acid sequences typical of β-strand conformations. Space-filling atomic models revealed that the β-strand sequences would permit the formation of 2-chain and 4-chain cylindrical β-helices, fully shielding the hydrophobic amino acid chains that alternate with hydrophilic residues in these sequences. Because of the locations of the β-helical regions in human and mouse stratum corneum keratin chains, only homodimers of the keratins could interact efficiently to form 2-chain and 4-chain β-helices. Tetramers having the directions and degrees of overlap of constituent dimers that have been identified by previous investigators are also predicted from the interactions of β-helical motifs. Heterotetramers formed from dissimilar homodimers could combine, through additional β-helical structures, to form higher oligomers having the dimensions seen in electron microscopic studies. Previous results from chemical crosslinking studies can be interpreted to support the concept of homodimers rather than heterodimers as the basis for keratin filament assembly. © 1995 Wiley-Liss, Inc. |
