Amyloidogenicity and cytotoxicity of des-Lys-1 human amylin provides insight into amylin self-assembly and highlights the difficulties of defining amyloidogenicity.
Protein Eng Des Sel
; 32(2): 87-93, 2019 12 13.
Article
em En
| MEDLINE
| ID: mdl-31768548
ABSTRACT
The polypeptide amylin is responsible for islet amyloid in type 2 diabetes, a process which contributes to ß-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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polipeptídeo Amiloide das Ilhotas Pancreáticas
/
Agregados Proteicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article