IAPP misfolding pathways. A: Schematic illustration of a stepwise misfolding pathway of IAPP that generates toxic oligomers as well as a range of different
fibril types. Although the structure of IAPP oligomers remains elusive, the crystal structure of an A11 antibody–positive
oligomer structure has recently been reported (25) and is shown in panel B. C and D: The reported structures for fibrils with striated ribbons and twisted morphologies. The bottom shows the structure of single
IAPP molecule (green). In case of the striated ribbon, the two strands are approximately in the same plane while the two strands
in the fibrils with twisted morphology are offset. Individual stacks of monomers were built using MFIBRIL (http://chemsoft.hsc.usc.edu:8080/MFIBRIL/) and colored green, brown, and blue. MFIBRIL was then used to dock individual stacks together to better mimic the fibril
structure (blue and magenta). Note that contacts in the striated ribbons are made between same monomeric subunits, whereas
contacts in the twisted fibrils are more staggered by packing strands from one monomer subunit against strands from a monomer
three layers above.