The bullous pemphigoid antigen BPAG1 is required for keratin filament linkage to the hemidesmosome, an adhesion complex in epithelial basal cells, BPAG1 structural organization is similar to the intermediate filament-associated proteins desmoplakin I (DPI) and plectin, All three proteins have predicted dumbbell-like structure with central alpha-helical coiled-coil rod and regions of N- and C-terminal homology, To characterize the size of the N-terminal globular domain in BPAG1, two polypeptides spanning possible boundaries with the coiled-coil rod domain of BPAG1 were expressed in Escherichia coli, BP-1 (M(r) = 111,000), containing amino acids 663-1581 of BPAG1 (Sawamura, D., Li, K., Chu, M.-L., and Uitto, J, (1991) J, Biol, Chem, 266, 17784-17790), and BP-1A, with a 186 amino acid N-terminal deletion, were purified, BP-1 and BP-1A behave as highly asymmetric dimers in aqueous solution according to velocity sedimentation and gel filtration, Both have globular heads with rod-like tails of roughly equal length, 55-60 nm, upon rotary shadowing, BP-1A content of cu-helix, determined by circular dichroism, is similar to 90%, consistent with alpha-helical coiled-coil formation in the rod-like tails, The estimated rod length, 383 +/- 57 amino acids (0.15 nm/amino acid), implies that globular folding in the BPAG1 N-terminal extends to the end of N-terminal homology with DPI and plectin. These findings support the existence of a common domain structure in the N-terminal regions of the BPAG1/DPI/plectin family.
