Single-molecule visualization determines conformational substate ensembles in β-sheet-rich peptide fibrils.

ABSTRACT: An understanding of protein conformational ensembles is essential for revealing the underlying mechanisms of interpeptide recognition and association. However, experimentally resolving multiple simultaneously existing conformational substates remains challenging. Here, we report the use of scanning tunneling microscopy (STM) to analyze the conformational substate ensembles of β sheet peptides with a submolecular resolution (in-plane <2.6 Å). We observed ensembles of more than 10 conformational substates (with free energy fluctuations between several k_BTs) in peptide homoassemblies of keratin (KRT) and amyloidal peptides (-5Aβ42 and TDP-43 341-357). Furthermore, STM reveals a change in the conformational ensemble of peptide mutants, which is correlated with the macr

SUBMITTER: Zhang W 

PROVIDER: S-EPMC10321740 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature