HOMOLOGY OF CALCITONIN WITH THE AMYLOID-RELATED PROTEINS

We present evidence for a structural homology between the amino acid s equence of calcitonin (CT) - the fibrillar protein of the amyloid depo sits of medullary thyroid cancer - and that of other 12 amyloid-relate d proteins (ARP). Seven of the 32 residues of CT are conserved in at l east five ARP, and five of these seven amino acids belong to the stret ch Gly2-Gln14. Gln14 is conserved in all 12 ARP and Cys7 in all eight ARP containing cysteine. The concentration of the homology in the N-te rminal half of CT goes along with the knowledge that is the C-terminal region the one more important for the hormonal action of CT. Since an imbalance between synthesis and catabolism of a given ARP is believed to be the general pathogenetic mechanism of amyloidosis, the intratum oral deposition of CT in the form of amyloid fibrils would be due to t he overproduction of a protein structurally similar to the ARP.