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

Xiao-Bo Mao, 

Chen-Xuan Wang, 

Xing-Kui Wu, 

Xiao-Jing Ma, 

Lei Liu, 

Lan Zhang, 

Lin Niu, 

Yuan-Yuan Guo, 

Deng-Hua Li, 

Yan-Lian Yang, and 

Chen Wang

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 Ser₁₉/Ser₂₀ and Gly₂₄. 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.

DOI

Journal: Proceedings of the National Academy of Sciences