biostudies-literatureYang TUKRI Medical Research CouncilMedical Research CouncilNational Institutes of HealthWellcome TrustNational Institute of General Medical SciencesNIGMS NIH HHS107168https://www.ebi.ac.uk/biostudies/studies/S-EPMC11223093biostudies-literatureUnknown307The polypeptide hormone Amylin (also known as islet amyloid polypeptide) plays a role in regulation of glucose metabolism, but forms pancreatic islet amyloid deposits in type 2 diabetes. The process of islet amyloid formation contributes to β-cell dysfunction and the development of the disease. Amylin is produced as a pro-from and undergoes processing prior to secretion. The mature hormone contains an amidated C-terminus. Analysis of an alignment of vertebrate amylin sequences reveals that the processing signal for amidation is strictly conserved. Furthermore, the enzyme responsible for C-terminal amidation is found in all of these organisms. Comparison of the physiologically relevant amidated form to a variant with a free C-terminus (Amylin-COO^-) shows that replacement of the CBiophysical chemistryOn the importance of being amidated: Analysis of the role of the conserved C-terminal amide of amylin in amyloid formation and cytotoxicity.PMC11223093R01 GM078114GM078114107927/Z/15/ZMR/T032154/1Filippov IZhyvoloup AManathunga LRaleigh DPYang TBaghai AMarechal AfalseOn the importance of being amidated: Analysis of the role of the conserved C-terminal amide of amylin in amyloid formation and cytotoxicity.The polypeptide hormone Amylin (also known as islet amyloid polypeptide) plays a role in regulation of glucose metabolism, but forms pancreatic islet amyloid deposits in type 2 diabetes. The process of islet amyloid formation contributes to β-cell dysfunction and the development of the disease. Amylin is produced as a pro-from and undergoes processing prior to secretion. The mature hormone contains an amidated C-terminus. Analysis of an alignment of vertebrate amylin sequences reveals that the processing signal for amidation is strictly conserved. Furthermore, the enzyme responsible for C-terminal amidation is found in all of these organisms. Comparison of the physiologically relevant amidated form to a variant with a free C-terminus (Amylin-COO^-) shows that replacement of the C2024-01-01T00:00:00Z2024 Apr2026-06-01T09:24:59.83Z2025-04-04T12:21:46.296ZS-EPMC112230933836754110.1016/j.bpc.2023.107168