Submolecular Resolution of β‑Sheet Plasticity: Decoding Mutations and PTMs in Protein Aggregation Disorders.

ABSTRACT: The functional diversity of proteins often arises from the remodeling of conformational ensembles, particularly through mutations and post-translational modifications (PTMs). However, experimentally characterizing such ensembles remains challenging due to their heterogeneous and transient nature. Here, we report the determination of the conformational substates of β-sheets and the effect associated with mutations and PTMs in human islet amyloid polypeptide (hIAPP) via scanning tunneling microscopy (STM). Thanks to the ultrahigh resolution of STM, the β-sheets formed by the assembly of hIAPP were revealed to be conformationally diverse, including 17 types of conformational substates concomitant with 60 types of interconformation interactions. These conformational substates are highly hetero

SUBMITTER: Wang R 

PROVIDER: S-EPMC12203261 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature