Characterization and purification of human corneodesmosin, an epidermal basic glycoprotein associated with corneocyte-specific modified desmosomes.

Using monoclonal antibodies, we identified a new protein in mammalian epidermis, which we called corneodesmosin. It is located in the extracellular part of the modified desmosomes in the cornified layer of the tissue, and its proteolysis (from 52-56 to 33 kDa) is thought to be a major prerequisite of desquamation. We have now further characterized human corneodesmosin. Proteolysis of purified cornified cell envelopes produced immunoreactive fragments, confirming the covalent linkage of the protein to these structures. Sequential extraction of epidermal proteins indicated that the 52-56-kDa precursor form of the protein exists in two distinct pools, one extracted with a nondenaturing hypotonic buffer, and the other with urea. Two-dimensional gel analysis and reactivity with phosphoserine-specific antibodies showed that it is a basic phosphoprotein. Deglycosylation experiments, reactivity with lectins, and chromatography on concanavalin A-Sepharose indicated that corneodesmosin is N-glycosylated. Partial sequences, 10 and 15 amino acids long, of the purified 52-56-kDa corneodesmosin showed identity with sequences predicted from a previously cloned gene, proved to be expressed in the epidermis and designated S. This indicates that corneodesmosin is probably encoded by the S gene, the function of which was unknown until now. A model of corneodesmosin maturation during cornification is proposed.