Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.

Détails

ID Serval
serval:BIB_7B1B7F3755A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.
Périodique
Journal of Biological Chemistry
Auteur(s)
Hohl D., Mehrel T., Lichti U., Turner M.L., Roop D.R., Steinert P.M.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
04/1991
Peer-reviewed
Oui
Volume
266
Numéro
10
Pages
6626-6636
Langue
anglais
Résumé
We have isolated and characterized a full-length cDNA clone encoding human loricrin. Curiously, this protein displays major differences from the recently described mouse loricrin (Mehrel, T., Hohl, D., Nakazawa, H., Rothnagel, J.A., Longley, M.A., Bundman, D., Cheng, C.K., Lichti, U., Bisher, M.E., Steven, A. C., Steinert, P.M., Yuspa, S.H., and Roop, D.R. (1990) Cell 61, 1103-1112). Although both proteins are glycine-serine-cysteine-rich, the sequences have not been conserved. However, analysis of the sequences reveals a common motif of quasi-peptide repeats of an aliphatic or aromatic amino acid residue followed by several glycine and/or serine and cysteine residues. These sequences are interspersed and flanked by short glutamine- or glutamine/lysine-rich peptides. Thus loricrins consist of a family of cell envelope proteins of highly variable sequences that nevertheless retain common structural elements. We show that unlike all other putative protein components of the cell envelope, loricrins are highly insoluble, due at least in part to cross-linking by disulfide bonds. Furthermore, we have isolated four peptides from purified human cell envelopes that contain recognizable loricrin sequences and which are cross-linked by the N epsilon-(gamma-glutamyl)lysine isodipeptide bond. The presence of such bonds thus affords an explanation for the extraordinary insolubility of loricrin by cross-linking to the cell envelope and can also explain the low steady-state levels of monomeric loricrin in cytoskeletal extracts of epidermis. This study represents the first report of this isodipeptide cross-link in a protein component of the cornified cell envelope. We propose a model for the structure of loricrin in which (i) the unusual glycine-serine-rich sequences adopt a flexible loop conformation, indexed on the recurrent aliphatic residues; (ii) inter- or intramolecular isodipeptide and disulfide cross-links induce or stabilize folding of loricrin so as to form a more compact rosette-like structure; and (iii) the presence of the flexible glycine-rich loops necessarily will impact a flexible character to the cell envelope and entire epithelium.
Mots-clé
Amino Acid Sequence, Amino Acids/analysis, Base Sequence, Blotting, Northern, DNA/genetics, Epidermis/metabolism, Fluorescent Antibody Technique, Humans, Membrane Proteins/genetics, Membrane Proteins/metabolism, Molecular Sequence Data, Nucleic Acid Hybridization, Protein Biosynthesis, RNA, Messenger/analysis, RNA, Messenger/genetics
Pubmed
Web of science
Création de la notice
25/01/2008 17:36
Dernière modification de la notice
20/08/2019 15:37
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