A Tetramer Derived from Islet Amyloid Polypeptide.

ABSTRACT: Aggregation of the islet amyloid polypeptide (IAPP) to form fibrils and oligomers is important in the progression of type 2 diabetes. This article describes X-ray crystallographic and solution-state NMR studies of peptides derived from residues 11-17 of IAPP that assemble to form tetramers. Incorporation of residues 11-17 of IAPP (RLANFLV) into a macrocyclic β-sheet peptide results in a monomeric peptide that does not self-assemble to form oligomers. Mutation of Arg₁₁ to the uncharged isostere citrulline gives peptide homologues that assemble to form tetramers in both the crystal state and in aqueous solution. The tetramers consist of hydrogen-bonded dimers that sandwich together through hydrophobic interactions. The tetramers share several features with structures reported for

SUBMITTER: Wang Y 

PROVIDER: S-EPMC7532939 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature