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Cover Picture: Dissecting the Role of Single Regions of an IAPP Mimic and IAPP in Inhibition of Aβ40 Amyloid Formation and Cytotoxicity (ChemBioChem 9/2011)
The cover picture shows the effects of individual regions of IAPP-GI, a nonamyloidogenic mimic of the type 2 diabetes islet amyloid polypeptide (IAPP), on amyloid formation of the Alzheimer's disease amyloid β-peptide (Aβ). IAPP-GI has previously been found to bind Aβ with high affinity and to block its cytotoxic amyloidogenesis. Moreover, the Aβ-IAPP cross-amyloid interaction suppresses cytotoxic self-association by both polypeptides and might be a molecular link between the two diseases. Here the 37-residue IAPP-GI was dissected into shorter segments including the two hot-spot regions of the Aβ-IAPP(IAPP-GI) interaction interface IAPP(8–18) (pink) and IAPP(22–28)-GI (green) and the N- or C-terminal regions IAPP(1–7) (light blue) and IAPP(30–37) (dark blue). Only IAPP-GI and IAPP(1–28)-GI inhibited Aβ cytotoxic self-assembly and amyloidogenesis whereas all other segments even the ones containing hot-spot regions, such as IAPP(8–28)-GI, were unable to inhibit uncovering thus important molecular determinants of the IAPP-GI(IAPP) mediated inhibition of Aβ self-assembly. For more details, see the paper by A. Kapurniotu et al. on p. 1313 ff.