POSTSYNTHETIC MODIFICATIONS OF MAMMALIAN EPIDERMAL ALPHA-KERATIN

The solubility and properties of the α-keratin polypeptides of the living cell layers and of serial slices through the stratum corneum of bovine and human epidermis, which reflect tissue of different ages after keratinization, have been compared. The yields and properties of the α-keratin polypeptides extracted from the living cell layers and inner stratum corneum slice were similar, except the former contained thiol groups and the latter intrachain disulfide bonds, as was shown by Steinert [Steinert, P. M. (1975) Biochem. J. 149, 39-48]. In contrast, in progression to the outer slice of stratum corneum, the polypeptides became less soluble, were cross-linked mostly by interchain disulfide bonds, had higher contents of α helix, contained significant amounts of free amino termini, and polymerized into native-type epidermal keratin filaments in vitro with diminished efficiency, and the relative molar amounts of the individual polypeptides were altered and in creasing amounts of the high molecular weight aggregates appeared. These aggregates contained the amino acid citrulline and were cross-linked by unusual compounds, three of which were identified as lanthionine, Є-(γ-glutamyl)lysine and lysi-noalanine and were present in total amounts approaching 1 mol/mol. These observations suggest that the α-keratin polypeptides in the epidermis undergo modifications after synthesis, such as initial oxidation to form intrachain and then rearrangement to form interchain disulfide bonds and the formation of Є-(γ-glutamyl)lysine cross-links. When the stratum corneum approaches the outer surface of the epidermis, however, the intracellular proteins undergo further modifications such as partial degradation and formation of cross-links under alkaline conditions that are presumably affected by exposure of the tissue to the rigors of the environment. © 1979, American Chemical Society. All rights reserved.