Cutaneous amyloidoses: A minimum common denominator in their amino acid sequence

摘要

Background: Peptides forming amyloid fibrils in cutaneous amyloidoses are derived from various precursors, often unrelated to each other. We aimed to identify an amino acid pattern shared by disease-relevant peptides associated with newly reported and already known cutaneous amyloidoses. Method: We probed proteins of cutaneous and non-cutaneous amyloidoses for the amyloid motif identified previously ("D/E/N/Q A/G, D/E/N/Q, 4-20X, V/I/L/M, D/E/N/Q, R/K/H, 0-6X, V/I/L/M, 0-5X, F/Y/W, 4-5X, D/E/N/Q, 0-2X, R/K/H, 0-12X, A/G, V/I/L/M, 0-3X, V/I/L/M, 0-2X, A/G"). Once segments containing the motif were found, these were subject to multiple alignment to detect similarities and dissimilarities between them.Results: The amyloid motif was present, totally or partially, in all proteins; in turn, it was contained, completely or incompletely, in segments of such proteins known to be deposited in the corresponding amyloidoses. The aligned segments of the cutaneous amiloidoses were more similar to each other than to those of the noncutaneous amyloidoses.Conclusions: The motif-based approach can contribute to the multidisciplinary solution of the complex problem of the pathogenesis of amyloidosis, and could help to identify possible new amyloid forming proteins.