Beta structure motifs of islet amyloid polypeptides identified through surface-mediated assemblies.

Abstract

We report here the identification of the key sites for the beta structure motifs of the islet amyloid polypeptide (IAPP) analogs by using scanning tunneling microscopy (STM). Duplex folding structures in human IAPP(8-37) (hIAPP(8-37)) assembly were observed featuring a hairpin structure. The multiplicity in rIAPP assembly structures indicates the polydispersity of the rat IAPP(8-37) (rIAPP(8-37)) beta-like motifs. The bimodal length distribution of beta structure motifs for rIAPP(8-37) R18H indicates the multiple beta segments linked by turns. The IAPP(8-37) analogs share common structure motifs of IAPP(8-17) and IAPP(26-37) with the most probable key sites at positions around Ser(19)/Ser(20) and Gly(24). These observations reveal the similar amyloid formation tendency in the C and N terminus segments because of the sequence similarity, while the differences in specific amino acids at each key site manifest the effect of sequence variations. The results could be beneficial for studying structural polymorphism of amyloidal peptides with multiple beta structure motifs.