Amyloidogenicity and cytotoxicity of des-Lys-1 human amylin provides insight into amylin self-assembly and highlights the difficulties of defining amyloidogenicity.

ABSTRACT: The polypeptide amylin is responsible for islet amyloid in type 2 diabetes, a process which contributes to ?-cell death in the disease. The role of the N-terminal region of amylin in amyloid formation is relatively unexplored, although removal of the disulfide bridged loop between Cys-2 and Cys-7 accelerates amyloid formation. We examine the des Lys-1 variant of human amylin (h-amylin), a variant which is likely produced in vivo. Lys-1 is a region of high charge density in the h-amylin amyloid fiber. The des Lys-1 polypeptide forms amyloid on the same time scale as wild-type amylin in phosphate buffered saline, but does so more rapidly in Tris. The des Lys-1 variant is somewhat less toxic to cultured INS cells than wild type. The implications for the in vitro mechanism of amyloid formation and for comparative analysis of amyloidogenicity are discussed.

SUBMITTER: Lee KH 

PROVIDER: S-EPMC6908818 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature