Structural Similarities and Differences between Amyloidogenic and Non-Amyloidogenic Islet Amyloid Polypeptide (IAPP) Sequences and Implications for the Dual Physiological and Pathological Activities of These Peptides
Figure 7
Schematic representation of misfolding/aggregation mechanism of hIAPP.
Left: Helix-coil structure for normal function; Middle: aggregation-prone β-rich monomers; Right: early putative toxic dimers (Dupuis et al. JACS 2011). The question mark indicates the hairpins may further form cylindrin-like toxic oligomers, modeled from the cylindrical barrel of an amyloid peptide (PDB id: 3SGR) (Laganowsky et al. Science 2012). The isomerization symbol indicates that at some, as yet unknown size, the β-strand aggregates must rearrange to the β-sheet aggregates found in the fibrils. N-terminus is indicated by red ball, residues 23–29 in the “mutation region” are in red. In the β-hairpin, residues 19S-20S-21N-22N form a turn and residues 11–19 and 23–33 form two β-strands.