Abstract
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.
Highlights
Bullous pemphigoidis a subepidermal blisteringdis- anchoring basal cells to the basement membrane [2,3,4]
bullous pemphigoid antigen (BPA) anddesmoplakin I, a desmosome plaque clone to isolate overlappingcDNAclonesencodingfor 243 kDa of BPA
Inaddition,each of these regions acid homology (Fig. 6) that is about of the same degree as that seen between BPA andmyosin, suggesting that it is due to the shared a-helical heptad substructuArse.the periodicity in the acidic and basic residues in the rod domain of both BPA and desmoplakin I (DPI) is similar (Table I),a potential means of selfaggregationfor each of these plaque proteins through the maximization of ionic interactions becomes self-evident [9]
Summary
University of Wisconsin Genetics Computer Group software [21] domain,most of the 1,162 residues are postulated to was used as follows: (i) the RPA amino acid sequence was compared form a discontinuous coiled-coil a-helical rod of the general for homologies against the NRRF version 25 protein database using typefound in paramyosin, myosin, andkeratin molecules. This conclusion According to the isbasedonthe following methodsof Chou and Fasand a stringency of 15) and plotted with DOTPLOT. Each of the two long rod domains (in contrast torod domains 1 and 2) havea highly significant periodic linear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
