The Structure of Human IAPP Fibrils Reflects Membrane and pH Conditions.

ABSTRACT: Physiologically relevant in vitro models of amyloid aggregation are essential for linking structural insights to disease pathology. In type 2 diabetes, aggregation of human islet amyloid polypeptide (hIAPP) into fibrils is a hallmark of β-cell dysfunction, yet structural data on ex vivo hIAPP fibrils remain unavailable. Most models use solution-grown fibrils, overlooking membrane interactions and native pH, which underscores the need for more realistic in vitro models. Here, we use solid-state NMR spectroscopy to determine the structure of phospholipid membrane-mediated hIAPP fibrils formed under extracellular (pH 7.4) conditions. These fibrils are homogeneous and adopt an L-shaped protofilament architecture with an extended N-terminal β-strand─a region often unresolved in cryo-EM. The fib

SUBMITTER: Mithu VS 

PROVIDER: S-EPMC12356532 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature