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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)
Author(s) -
Andreetto Erika,
Yan LiMei,
Caporale Andrea,
Kapurniotu Aphrodite
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201190036
Subject(s) - chemistry , amyloid (mycology) , cytotoxicity , biochemistry , peptide , cytotoxic t cell , islet , biophysics , biology , in vitro , endocrinology , diabetes mellitus , inorganic chemistry
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.