Hard alpha-keratin IF: a structural model lacking a head-to-tail molecular overlap but having hybrid features characteristic of both epidermal keratin and vimentin IF.
In intermediate filaments (IF) both epidermal keratin and vimentin molecules have been shown to have an eight residue head-to-tail overlap between the rod domains of similarly directed molecules. In the case of the epidermal keratins this region has also been shown to have particular structural/functional significance since it represents a hot-spot for mutations in the four keratinopathies characterized to date. While there is good evidence that this head-to-tail overlap is present in IF containing Type III, IV, and V chains, as well as in the epidermal keratin IF (Ib/IIb), there are no data currently available for the hard alpha-keratin IF (Ia/IIa). Using a variety of data derived from X-ray diffraction and crosslinking studies, as well as theoretical modeling, it is now possible to demonstrate that the overlap region is not a feature of hard alpha-keratin IF. Indeed, it is shown that there is a nine residue gap between consecutive parallel molecules in the IF. An explanation for this observation is presented in terms of compensating disulfide bonds that occur both within the IF, and between the IF and the matrix in which the IF are embedded.
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D004817:Epidermis / Q000737:chemistry*; D006801:Humans; D007382:Intermediate Filaments / Q000737:chemistry*; D007633:Keratins / Q000737:chemistry*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014746:Vimentin / Q000737:chemistry*
D004220:Disulfides; D014746:Vimentin; D007633:Keratins