Experimental Insights into Conformational Ensembles of Assembled β-Sheet Peptides

Lanlan Yu 1, Ruonan Wang 1, Shucong Li 2, Ufuoma I Kara 3, Eric C Boerner 3, Boyuan Chen 3, Feiyi Zhang 1 4, Zhongyi Jian 1, Shuyuan Li 1, Mingwei Liu 1, Yang Wang 1, Shuli Liu 5, Yanlian Yang 6, Chen Wang 6, Wenbo Zhang 1, Yuxing Yao 7, Xiaoguang Wang 3 8, Chenxuan Wang 1

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ACS Cent Sci.2023 Jul 4;9(7):1480-1487.

PMID: 37521785

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Abstract

Deciphering the conformations and interactions of peptides in their assemblies offers a basis for guiding the rational design of peptide-assembled materials. Here we report the use of scanning tunneling microscopy (STM), a single-molecule imaging method with a submolecular resolution, to distinguish 18 types of coexisting conformational substates of the β-strand of the 8-37 segment of human islet amyloid polypeptide (hIAPP 8-37). We analyzed the pairwise peptide-peptide interactions in the hIAPP 8-37 assembly and found 82 interconformation interactions within a free energy difference of 3.40 kBT. Besides hIAPP 8-37, this STM method validates the existence of multiple conformations of other β-sheet peptide assemblies, including mutated hIAPP 8-37 and amyloid-β?42. Overall, the results reported in this work provide single-molecule experimental insights into the conformational ensemble and interpeptide interactions in the β-sheet peptide assembly.