Elucidating the multi-targeted anti-amyloid activity and enhanced islet amyloid polypeptide binding of <i>β</i>-wrapins.

ABSTRACT: β-wrapins are engineered binding proteins stabilizing the β-hairpin conformations of amyloidogenic proteins islet amyloid polypeptide (IAPP), amyloid-β, and α-synuclein, thus inhibiting their amyloid propensity. Here, we use computational and experimental methods to investigate the molecular recognition of IAPP by β-wrapins. We show that the multi-targeted, IAPP, amyloid-β, and α-synuclein, binding properties of β-wrapins originate mainly from optimized interactions between β-wrapin residues and sets of residues in the three amyloidogenic proteins with similar physicochemical properties. Our results suggest that IAPP is a comparatively promiscuous β-wrapin target, probably due to the low number of charged residues in the

SUBMITTER: Orr AA 

PROVIDER: S-EPMC6217933 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature