Comparison of molecularly cloned bullous pemphigoid antigen to desmoplakin I confirms that they define a new family of cell adhesion junction plaque proteins

• Published in: The Journal of biological chemistry Vol. 266; no. 19; pp. 12555 - 12559
• Main Authors: TANAKA, T, PARRY, D. A. D, KLAUS-KOVTUN, V, STEINERT, P. M, STANLEY, J. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05.07.1991
• Subjects: Amino Acid Sequence; Autoantigens - genetics; autoimmune diseases; Biological and medical sciences; Blotting, Northern; Bullous diseases of the skin; Carrier Proteins; Cell Adhesion - genetics; Cloning, Molecular; Collagen; Collagen Type XVII; Cytoskeletal Proteins - immunology; Dermatology; desmoplakin I; Desmoplakins; Desmosomes - immunology; DNA - genetics; Dystonin; Humans; Medical sciences; Molecular Sequence Data; Nerve Tissue Proteins; Non-Fibrillar Collagens; Nucleic Acid Hybridization; Open Reading Frames; pemphigoid; Pemphigoid, Bullous - immunology; RNA - analysis; Sequence Homology, Nucleic Acid; skin diseases; Bullous dermatosis; Antigen; Human; Proteins; Immunopathology; Skin disease; Bullous pemphigoid; Autoimmune disease; Homology; Primary structure; Desmosome; Molecular cloning
• DOI: 10.1016/S0021-9258(18)98934-9
• ISSN: 0021-9258

Bullous pemphigoid is a subepidermal blistering disease in which patients have autoantibodies against the plaque of the hemidesmosome. Starting with a previously isolated 2-kilobase (kb) cDNA for bullous pemphigoid antigen (BPA), we used primer extension of keratinocyte mRNA to isolate overlapping cDNAs with a combined open reading frame of 6.3 kb, encoding most (243 kDa) of the BPA, but lacking the far amino terminus. Analysis of this amino acid sequence revealed a carboxyl-terminal domain containing two regions of 174 and 176 residues with high sequence identity. Most of the amino-terminal two-thirds of BPA is predicted to be in an alpha-helical conformation in which two chains would aggregate into a coiled-coil rod structure. BPA and desmoplakin I, a desmosome plaque protein, show remarkable sequence and structural homology. In its carboxyl-terminal domain, desmoplakin I also has 176 residue repeats with 40% sequence identity to those in BPA. The repeats in both molecules have a regular linear distribution of acidic and basic residues with a period of 9.5, the same as that found in the 1B segment of keratin filaments, suggesting a means of ionic interaction between keratin and these plaque proteins. Also, desmoplakin I, like BPA, is predicted to have a rod domain, which in both proteins has similar regular charge periodicities, suggesting a means of ionic self-aggregation. These findings extend those of Green et al. (Green, K. J., Parry, D. A. D., Steinert, P. S., Virata, L. A., Wagner, R. M., Angst, B. D., and Nilles, L. A. (1990) J. Biol. Chem. 265, 2603-2612) which show that BPA and desmoplakin I represent the first members of a new family of adhesion junction plaque proteins.