Sequence homology of parathyroid hormone against amyloidogenic regions of proteins

Excerpt

A number of peptide hormones or thyroid hormone-binding plasma proteins are involved in forms of systemic or localized amyloidosis [1, 2]. These amyloid-related hormones include atrial natriuretic factor, calcitonin, insulin, amylin (islet amyloid polypeptide), and prolactin, while amyloid-related thyroid hormone plasma carriers include transthyretin and apolipoproteins A-I, A-II, and A-IV. Our group had previously shown [2‐7] that the amyloid-forming peptides of the abovementioned proteins have amino acid sequence homology with the other fibrillar amyloidogenic proteins and that a general consensus motif can be generated. Based on our last article [2], this general consensus motif is “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” (where amino acids are in one-letter code and X indicates any amino acid). Thus, for instance, sequence 34–66 of amylin (precursor number, corresponding to 1–33 in the mature protein), i.e., “KCNTATCATQRLANFLVHSSNNFGAILSSTNVG,” matches at 8/14 positions the general “amyloid motif,” and such matches are indicated by the boldface print and underlined. …